1. Central Nervous System Development
David L. McWhorter, Ph.D.

2. Nervous System Consists of Three Main Parts
Central nervous system (CNS):
brain and spinal cord
Peripheral nervous system (PNS):
neurons outside the CNS
cranial and spinal nerves
connect brain and spinal cord with peripheral structures
Autonomic nervous system (ANS):
has parts in both the CNS and PNS
consists of neurons that innervate:
smooth muscle, cardiac muscle, and glandular epithelium

3. Origin of the Nervous System
Develops from the neural plate:
Dorsal thickened area of embryonic ectoderm
Neural folds:
elevated lateral margins of neural plate
Neural groove:
longitudinal midline depression of neural plate
Neural tube differentiates into:
CNS (brain and spinal cord)
Neural crest:
Some cells from apices of neural folds become separated to form dorsolateral groups and gives rise to:
Cells that form most of PNS and ANS (cranial, spinal, and autonomic ganglia)
Transverse section
Dorsal view, ~ 17 days, amnion removed
Notochord and paraxial mesenchyme induce overlying ectoderm to differentiate into neural plate
Illustrations of the neural plate and folding of it to form the neural tube.
A, Dorsal view of an embryo of approximately 17 days, exposed by removing the amnion.
B, Transverse section of the embryo showing the neural plate and early development of the neural groove and neural folds.
C, Dorsal view of an embryo of approximately 22 days. The neural folds have fused opposite the fourth to sixth somites, but are spread apart at both ends.
D to F, Transverse sections of this embryo at the levels shown in C illustrating formation of the neural tube and its detachment from the surface ectoderm (primordium of epidermis). Note that some neuroectodermal cells are not included in the neural tube, but remain between it and the surface ectoderm as the neural crest.
Signaling molecules involve members of the transforming growth factor β family, Shh, and BMPs.
Transverse sections
Dorsal view, ~22 days

4. Neurulation
Formation of neural plate and subsequent formation of neural tube and neural crest
Begins at days of development:
in region of fourth to sixth pairs of somites
At this stage:
cranial two-thirds of neural plate and tube (as far caudal as fourth pair of somites) represent future brain
caudal one third of the neural plate and tube represents future spinal cord
Fusion of neural folds forms neural tube
proceeds in cranial and caudal directions
small areas of tube remain open at both ends
Know process by which neural tube forms =
Neural fold come together to form neural tube
Know nervous system (neural tube and crests) come from ectoderm
Do not worry about time line

5. Neural Tube Lumen is called neural canal
communicates freely with amniotic cavity
forms:
ventricular system of brain
central canal of spinal cord
Cranial opening is called rostral neuropore
closes on approximately day 25
Caudal opening is called caudal neuropore
closes about 2 days later
Closure of Neuropores
Coincides with establishment of blood vascular circulation for neural tube
Neural Tube
Lateral view, ~24 days
Dorsal view, ~23 days
Important: The center opening of the neural tube = neural canal  becomes ventricular system in the brain and the central canal in the spinal cord
As the neural tube folds to become a neural tube, there is an opening and the rostal and caudal end (closes from rostal caudal). Neurological disorders associated with this.
A, Dorsal view of an embryo of approximately 23 days showing fusion of the neural folds, forming the neural tube.
B, Lateral view of an embryo of approximately 24 days showing the forebrain prominence and closing of the rostral neuropore.
C, Diagrammatic sagittal section of the embryo showing the transitory communication of the neural canal with the amniotic cavity (arrows).
D, Lateral view of an embryo of approximately 27 days. Note that the neuropores shown in B are closed.
Lateral view, ~ 27 days

6. Walls of Neural Tube Thicken to form: Three primary brain vesicles:
brain and spinal cord
Three primary brain vesicles:
Forebrain
Midbrain
Hindbrain
Five secondary brain vesicles:
Telencephalon
Diencephalon
Mesencephalon
Metencephalon
Myelencephalon
lateral view, ~28 days
Transverse section
THE MOST IMPORTANT TOPIC OF THE LECTURE (intro to stuff to focus on)
After the formation of the neural tube, you get dilations along the neural tube = forebrain, midbrain, and hindbrain  become 5 vesicles  adult derivaties
A, Schematic lateral view of an embryo of approximately 28 days showing the three primary brain vesicles: forebrain, midbrain, and hindbrain. Two flexures demarcate the primary divisions of the brain.
B, Transverse section of this embryo showing the neural tube that will develop into the spinal cord in this region. The spinal ganglia derived from the neural crest are also shown.
C, Schematic lateral view of the central nervous system of a 6-week embryo showing the secondary brain vesicles and pontine flexure. The flexure occurs as the brain grows rapidly.
6-week embryo, showing secondary brain vesicles

7. Development of the Spinal Cord

8. Introduction
Neural tube caudal to fourth pair of somites develops into spinal cord
A, Schematic lateral view of an embryo of approximately 28 days showing the three primary brain vesicles: forebrain, midbrain, and hindbrain. Two flexures demarcate the primary divisions of the brain.
B, Transverse section of this embryo showing the neural tube that will develop into the spinal cord in this region. The spinal ganglia derived from the neural crest are also shown.
C, Schematic lateral view of the central nervous system of a 6-week embryo showing the secondary brain vesicles and pontine flexure. The flexure occurs as the brain grows rapidly.

9. Lateral Walls of Neural Tube
Thicken, gradually reducing size of neural canal
only a minute central canal is present at 9 to 10 weeks
Initially, neural tube wall is composed of:
pseudostratified, columnar neuroepithelium
Transverse section, ~ 23 days
In regards to the brain and the spinal cord, Neuroepithelial cells  all the nerves in CNS
Illustrations of the development of the spinal cord.
A, Transverse section of the neural tube of an embryo of approximately 23 days.
B and C, Similar sections at 6 and 9 weeks, respectively.
D, Section of the wall of the neural tube shown in A.
E, Section of the wall of the developing spinal cord showing its three zones.
In A to C, note that the neural canal of the neural tube is converted into the central canal of the spinal cord.
9 Weeks

10. Neuroepithelial Cells Constitute The Ventricular Zone (Ependymal Layer)
Gives rise to:
all neurons and macroglial cells in spinal cord
Neuroepithelial cells (both brain and spinal cord) 
-give rise to neuroblast  neurons
-give rise to macroglial cells (both astrocytes – in blood brain barrier, and oligodendrocytes – make myelin in CNS)
-give rise to ependymal cells – with pia matter make up choroid plexus, which is what synthesizes and releases CSF
so, neuroepithelial cells gives rise to everything in CNS EXCEPT microglial cells
Messenchymal cells in bone marrow  Microglial cells = macrophage of CNS
3 areas of neuroepithelial cells = ventricular zone (closest to the central canal), intermediate zone, and outer (marginal) zone
pseudostratified, columnar neuroepithelium  one layer of cells, but nuclei in different positions so looks like multi-layered appearance
Illustrations of the development of the spinal cord.
A, Transverse section of the neural tube of an embryo of approximately 23 days.
B and C, Similar sections at 6 and 9 weeks, respectively.
D, Section of the wall of the neural tube shown in A.
E, Section of the wall of the developing spinal cord showing its three zones.
In A to C, note that the neural canal of the neural tube is converted into the central canal of the spinal cord.

11. Two Other Layers of Developing Spinal Cord Wall
Outermost layer, marginal zone:
gradually becomes white matter (substance) of spinal cord
axons grow into it from nerve cell bodies in the spinal cord, spinal ganglia, and brain
Intermediate zone (mantle layer) consists of neuroepithelial cells that differentiate into primordial neurons called neuroblasts:
Become neurons as they develop cytoplasmic processes
Important: Know that different zones of neuroepithelial cells will become specialized into different things in both the brain and the spinal cord and migrate into two separate plates:
Alar plate
Basal plate
These plates represent congregations of neuroepithelial cells that either become specalized into sensory or motor function
- note: he didn’t really say he cared too much about what the marginal or intermediate zone did
Illustrations of the development of the spinal cord. A, Transverse section of the neural tube of an embryo of approximately 23 days. B and C, Similar sections at 6 and 9 weeks, respectively. D, Section of the wall of the neural tube shown in A. E, Section of the wall of the developing spinal cord showing its three zones. In A to C, note that the neural canal of the neural tube is converted into the central canal of the spinal cord.

12. Glioblasts (Spongioblasts)
Primordial supporting cells of CNS
Differentiate from neuroepithelial cells
mainly after neuroblast formation has ceased
Migrate from ventricular zone into:
intermediate and marginal zones
Some glioblasts become:
astroblasts and later astrocytes
Other glioblasts become oligodendroblasts and eventually oligodendrocytes
Know comes from neuroepithelial cells

13. Microglial Cells (Microglia)
Small cells derived from mesenchymal cells
Scattered throughout gray and white matter
Invade CNS in late fetal period after it has been penetrated by blood vessels
Originate in bone marrow
are part of mononuclear phagocytic cell population

14. Development Of The Spinal Cord
Dorsal and ventral midline portions of neural tube form:
thin roof- and floor-plates that serve as:
pathways for nerve fibers crossing from one side to the other
Lateral wall thickening produces a shallow longitudinal groove on each side called sulcus limitans that separates:
dorsal part, alar plate later associated with afferent or sensory functions
ventral part, basal plate later associated with efferent or motor functions
Disappears in adult spinal cord
Retained in rhomboid fossa of brain stem (4th ventricle floor)
Important slide
In the center, where the neural canal is, on the sides of the canal, have plates of neuroepithelial cells that migrate either dorsally or ventrally on either side of the developing spinal cord:
Alar plates: form dorsal horn of spinal cord
Collections of cell bodies associated with sensory function
Basal plates: form ventral horn of spinal cord and the lateral horns of the spinal cord
Ventral horns - Collections of cell bodies associated with motor function
Lateral horns – T1 – L2/3 give rise to presynaptic sympathetic fibers (intermediolateral cell columns)
Sulcus limitans = histological landmark that divides the alar and basal plates
It is a longitudinal group
Divides motor and sensory parts of the gray matter

15. Alar (Sensory) Plates
Cell bodies in the alar plates form dorsal gray horns that consist of:
Afferent nuclei
As alar plates enlarge, dorsal median septum forms
In brainstem  will divide into groups of sensory neurons
Collections of cell bodies = nuclei

16. Basal (Motor) Plates
Cell bodies in the basal plates form ventral and lateral gray horns that contain:
Efferent nuclei
Basal plate axons grow out of spinal cord and form:
ventral roots of spinal nerves
As basal plates enlarge, they form a deep longitudinal groove:
ventral median fissure

17. Development of the Spinal Ganglia
Unipolar neurons in the spinal ganglia (dorsal root ganglia) are derived from neural crest cells
Axons of spinal ganglia cells are at first bipolar, but the two processes unite in a T-shaped fashion:
Both processes have structural characteristics of axons
Peripheral process is functionally a dendrite:
conduction from sensory endings in somatic or visceral structures toward cell body
Central process enter spinal cord and constitute:
dorsal roots of spinal nerves
Neural crest cells  bipolar neuroblast  psuedounipolar
Psuedounipolar cells make up the DRG. They are were the first synapse occurs. Before the synapse occurs in the DRG, as the conduction of the signal is running up towards the spinal nerve through some sense (sensory ends), it is the peripheral process until it reaches the cell body (DRG)  synapse occurs  enters the spinal cord = central process (through the dorsal roots of the spinal nerve
Diagrams showing some derivatives of the neural crest. Neural crest cells also differentiate into the cells in the afferent ganglia of cranial nerves and many other structures (see Chapter 5). The formation of a spinal nerve is also illustrated.

18. Development of the Spinal Meninges
Mesenchyme surrounding the neural tube condenses to form:
a membrane called the primordial meninx (L., membrane) or meninges
A, Dorsal view of an embryo of approximately 23 days showing fusion of the neural folds, forming the neural tube. B, Lateral view of an embryo of approximately 24 days showing the forebrain prominence and closing of the rostral neuropore. C, Diagrammatic sagittal section of the embryo showing the transitory communication of the neural canal with the amniotic cavity (arrows). D, Lateral view of an embryo of approximately 27 days. Note that the neuropores shown in B are closed.

19. Primordial Meninx or Meninges
External layer of this membrane thickens to form:
dura mater (pachymeninx; G., thick)
Internal layer derived from neural crest cells is the pia-arachnoid, composed of pia mater and arachnoid mater (leptomeninges; G., slender, delicate, weak)
Diagrams showing the position of the caudal end of the spinal cord in relation to the vertebral column and meninges at various stages of development. The increasing inclination of the root of the first sacral nerve is also illustrated. A, At 8 weeks. B, At 24 weeks. C, Newborn. D, Adult.

20. Leptomeninges Fluid-filled spaces coalesce to form:
subarachnoid space
Origin of pia mater and arachnoid from a single layer is indicated in the adult by:
arachnoid trabeculae
delicate strands of connective tissue that pass between pia and arachnoid
Cerebrospinal fluid (CSF) begins to form during fifth week
Diagrams showing the position of the caudal end of the spinal cord in relation to the vertebral column and meninges at various stages of development. The increasing inclination of the root of the first sacral nerve is also illustrated. A, At 8 weeks. B, At 24 weeks. C, Newborn. D, Adult.

21. Positional Changes of Spinal Cord
Initially, embryo spinal cord extends entire length of vertebral canal
Spinal nerves pass through intervertebral foramina opposite their levels of origin
Vertebral column and dura mater grow more rapidly than the spinal cord, changing positional relationship to spinal nerves
Caudal end of spinal cord gradually comes to lie at relatively higher levels
6-month-old fetus, spinal cord lies at first sacral vertebra level
Diagrams showing the position of the caudal end of the spinal cord in relation to the vertebral column and meninges at various stages of development. The increasing inclination of the root of the first sacral nerve is also illustrated. A, At 8 weeks. B, At 24 weeks. C, Newborn. D, Adult.
8 wks – entire vertebral column
24 wks – ends at S1
8 weeks
24 weeks
increasing inclination of the root of the first sacral nerve

22. Newborn and Adult Spinal Cord
Newborn spinal cord:
Terminates second or third lumbar vertebra level
Adult spinal cord:
Usually terminates at inferior border of first lumbar vertebra:
caudal end may be as superior as 12th thoracic vertebra or as inferior as third lumbar vertebra
As a result, spinal nerve roots (especially lumbar and sacral segments) run:
obliquely from spinal cord to corresponding level of vertebral column
Nerve roots inferior to end of cord are called medullary cone (L., conus medullaris)
form a bundle of spinal nerve roots called cauda equina (L., horse's tail)
dura mater and arachnoid mater usually end at S2 vertebra in adults
pia mater ends at conus medullaris
Diagrams showing the position of the caudal end of the spinal cord in relation to the vertebral column and meninges at various stages of development. The increasing inclination of the root of the first sacral nerve is also illustrated. A, At 8 weeks. B, At 24 weeks. C, Newborn. D, Adult.
Spinal cord ends L1/L2 postnatally = conus medullaris
Newborn
Adult

23. Caudal End of Spinal Cord
Distal to caudal end, pia mater forms a long fibrous thread:
terminal filum (L., filum terminale):
indicates original caudal end of embryonic spinal cord
extends from medullary cone and attaches to periosteum of first coccygeal vertebra
End of pia matter = filum terminal  internal and external component that anchor the spinal cord to the dura sac
Once spinal ends  cauda equina (horses tail, where nerves exit because there is more nerves for the vertebral levels that still need to come out)

24. Myelination of Nerve Fibers
Myelin sheaths surrounding nerve fibers within spinal cord begin to form during late fetal period
continue to form during first postnatal year
In general, fiber tracts become myelinated at approximately the time they become functional
Myelin basic proteins:
a family of related polypeptide isoforms, essential in myelination
Motor roots are myelinated before sensory roots
Diagrammatic sketches illustrating myelination of nerve fibers. A to E, Successive stages in the myelination of an axon of a peripheral nerve fiber by a neurolemmal cell. The axon first indents the cell; the cell then rotates around the axon as the mesaxon (site of invagination) elongates. The cytoplasm between the layers of the cell membrane gradually condenses. Cytoplasm remains on the inside of the sheath between the myelin and axon. F to H, Successive stages in the myelination of a nerve fiber in the central nervous system by an oligodendrocyte. A process of the neuroglial cell wraps itself around an axon, and the intervening layers of cytoplasm move to the body of the cell.

25. Myelin Sheaths
Surrounding nerve fibers within spinal cord are formed by oligodendrocytes
Plasma membranes of oligodendrocytes wrap around many axons:
forming a number of layers
Myelin sheaths around peripheral nerve axons are formed by:
plasma membranes of neurolemma cells (Schwann cells)
Envelop only part of one axon
Derived from neural crest cells
Diagrammatic sketches illustrating myelination of nerve fibers. A to E, Successive stages in the myelination of an axon of a peripheral nerve fiber by a neurolemmal cell. The axon first indents the cell; the cell then rotates around the axon as the mesaxon (site of invagination) elongates. The cytoplasm between the layers of the cell membrane gradually condenses. Cytoplasm remains on the inside of the sheath between the myelin and axon. F to H, Successive stages in the myelination of a nerve fiber in the central nervous system by an oligodendrocyte. A process of the neuroglial cell wraps itself around an axon, and the intervening layers of cytoplasm move to the body of the cell.
Schwann cells migrate peripherally and wrap themselves around:
axons of somatic motor neurons
preganglionic autonomic motor neurons
Also wrap themselves around:
central and peripheral processes of somatic and visceral sensory neurons
axons of postsynaptic autonomic motor neurons
Beginning at approximately 20 weeks, peripheral nerve fibers:
have a whitish appearance, resulting from deposition of myelin

26. Development of the Brain

27. Neural Tube Cranial to fourth pair of somites develops into brain
Fusion of neural folds in the cranial region and closure of the rostral neuropore form:
three primary brain vesicles from which the brain develops…
When neural tube forms, there are three enlargements of the neural tube that lead to 5 vesicles.
The three enlargements going from rostal  caudal = forebrain (prosencephlanon) , midbrain (mesencephalon), and hindbrain (rhombencephalon) = KNOW
Diagrammatic sketches of the brain vesicles indicating the adult derivatives of their walls and cavities. *The rostral part of the third ventricle forms from the cavity of the telencephalon; most of this ventricle is derived from the cavity of the diencephalon.

28. During Fifth Week: Five Secondary Brain Vesicles
Forebrain partly divides into:
Telencephalon
Diencephalon
Midbrain does not divide
Hindbrain partly divides into:
Metencephalon
Myelencephalon
THE MOST IMPORTANT SLIDE – memorize
Tel: G., end
Di: G., through
Mes: G., middle
Met: G., after
Myel: G., medulla, marrow

29. Brain Flexures (slide 1 of 2)
During fourth week, embryonic brain grows rapidly and bends ventrally with head fold, producing:
midbrain (cephalic) flexure in the midbrain region:
located between prosencephalon and rhombencephalon
cervical flexure at junction of hindbrain and spinal cord
Later, unequal growth of brain between cephalic and cervical flexures produces:
pontine flexure in the opposite direction
Located between metencephalon and myelencephalon
Results in thinning of hindbrain roof
4-5 weeks
Brain flexures  occur in different parts of the rostal nerual tube:
Effect the position of the brains white matter
Have considerable variations seen on cross sections
Didn’t say much about this
7-8 Weeks

30. Brain Flexures (slide 2 of 2)
Initially, primordial brain has same basic structure as developing spinal cord
Brain flexures produce:
considerable variation in outline of transverse sections at different levels of the brain
position of the gray and white matter (substance)
Sulcus limitans extends cranially to:
junction of midbrain and forebrain
Alar and basal plates recognizable only in midbrain and hindbrain
Didn’t say much about this
A, Sketch of the developing brain at the end of the fifth week showing the three primary divisions of the brain and the brain flexures. B, Transverse section of the caudal part of the myelencephalon (developing closed part of the medulla). C and D, Similar sections of the rostral part of the myelencephalon (developing open part of the medulla) showing the position and successive stages of differentiation of the alar and basal plates. The arrows in C show the pathway taken by neuroblasts from the alar plates to form the olivary nuclei.

31. Hindbrain Cervical flexure demarcates:
hindbrain from spinal cord
Later, this junction is defined as:
level of superior rootlet of first cervical nerve
located roughly at foramen magnum
Pontine flexure divides hindbrain into:
caudal (myelencephalon)
becomes medulla oblongata (often called medulla)
rostral (metencephalon)
becomes pons and cerebellum
Cavity of hindbrain becomes:
fourth ventricle
central canal in the medulla
Didn’t say much about this
A, Sketch of the developing brain at the end of the fifth week showing the three primary divisions of the brain and the brain flexures. B, Transverse section of the caudal part of the myelencephalon (developing closed part of the medulla). C and D, Similar sections of the rostral part of the myelencephalon (developing open part of the medulla) showing the position and successive stages of differentiation of the alar and basal plates. The arrows in C show the pathway taken by neuroblasts from the alar plates to form the olivary nuclei.

32. Lecture Summary (slide 1 of 3)
The CNS develops from?
Dorsal thickening of ectoderm-the neural plate that appears around the middle of the third week
The neural plate is induced by?
The underlying notochord and paraxial mesenchyme
The neural plate becomes infolded to form?
A neural groove that has neural folds on each side
When the neural folds fuse, it forms?
The neural tube
Some neuroectodermal cells are not included in the neural tube, but remain between the neural tube and surface ectoderm as?
The neural crest

33. Lecture Summary (slide 2 of 3)
The cranial end of the neural tube forms?
The brain; primordia of the forebrain, midbrain, and hindbrain
The forebrain gives rise to?
The cerebral hemispheres and diencephalon
The embryonic midbrain becomes?
The adult midbrain
The hindbrain gives rise to?
The pons, cerebellum, and medulla oblongata
The remainder of the neural tube becomes?
The spinal cord

34. Lecture Summary (slide 3 of 3)
The neural canal, the lumen of the neural tube, becomes?
The ventricles of the brain and the central canal of the spinal cord
The walls of the neural tube thicken by proliferation of its?
Neuroepithelial cells
Neuroepithelial cells give rise to?
All nerve and macroglial cells in the CNS
The microglia differentiate from?
Mesenchymal cells that enter the CNS with the blood vessels

35. Brainstem Development
Brainstem Primary Vesicles
Brainstem Secondary Vesicles
Derivatives in mature brain
Mesencephalon
MIDBRAIN
Rhombencephalon (Hindbrain)
Metencephalon
Ponds and cerebellum
myelencephalon
medulla

36. Posterior view of posterior portion of the spinal cord and the back of the brain stem (cerebellum removed)
Long nuclei = columns

37. Match Nerve Fiber Types with Functions
General Somatic Afferent (GSA) fibers
General somatic efferent (GSE) fibers
General visceral afferent (GVA) fibers
General visceral efferent (GVE) fibers
Transmit impulses to smooth and cardiac muscle and glandular tissues
Transmit reflex or pain from mucous membranes, glands, and blood vessels back to CNS
Transmit sensations from body to spinal cord (eg., pain, temperature, touch, & pressure)
Transmit impulses to skeletal muscles
1 = C
2 = D
3 = B
4 = A

38. Seven Types of Nerve Fibers Associated with Cranial Nerves
Motor (3):
General Somatic Efferent (GSE)
Special Visceral Efferent (SVE)
General Visceral Efferent (GVE)
Sensory (4):
General Visceral Afferent (GVA)
General Somatic Afferent (GSA)
Special Visceral Afferent (SVA)
Special Somatic Afferent (SSA)
Know this slide
Not all 12 cranial nerves have all of these, these are just all the possibilities that could be involved with a cranial nerve

39. Cranial Nerves: Motor Fibers (3)
Two subtypes of motor fibers to voluntary (striated) muscle based on embryologic origin:
General Somatic Efferent (GSE) axons innervate muscles derived from sources other than embryonic pharyngeal arches:
ocular muscles, tongue, external neck muscles (sternocleidomastoid and trapezius)
Special Visceral Efferent (SVE) axons innervate muscles derived from the embryonic pharyngeal arches (branchial motor):
face, palate, pharynx, and larynx
General Visceral Efferent (GVE) axons innervate involuntary (smooth) muscles or glands:
cranial outflow of parasympathetic division of ANS
Know this slide
2. = generally involved with CN V and VII

40. Cranial Nerves: Sensory Fibers (4)
General Visceral Afferent (GVA) axons carry sensation from the viscera:
Carotid body and sinus, pharynx, larynx, trachea, bronchi, lungs, heart, gastrointestinal tract
General Somatic Afferent (GSA) transmit general sensation from the skin and mucous membranes:
Touch, pressure, heat, cold
Two subtypes of fibers transmitting unique sensations:
Special Visceral Afferent (SVA) axons convey taste and smell
Special Somatic Afferent (SSA) axons convey vision, hearing and balance
Know this slide
Smell – CN I, taste CN VII, vision CN II, hearing and balance CN VIII

41. Caudal Myelencephalon
Caudal part (Closed part of medulla) resembles spinal cord (developmentally and structurally)
Neural canal of neural tube forms:
small central canal of myelencephalon
Neuroblasts from alar plates migrate into marginal zone and form isolated areas of gray matter:
gracile nuclei, medially
cuneate nuclei, laterally
Gracile and cuneate nuclei are associated with correspondingly named tracts that enter medulla from spinal cord
Ventral area of medulla contains:
pair of fiber bundles called the pyramids
consist of corticospinal fibers descending from developing cerebral cortex O C
As you develop cranially, the neural canal in the medualla closes and moves dorsally
Know alar plate moves dorsally and forms two collections on both sides  form specific nuclei = gracile and cuneate nucleus  deals with somatosensory proception

42. Rostral Myelencephalon
Rostral part (“Open" part of medulla) is wide and rather flat (especially opposite pontine flexure)
Pontine flexure causes:
lateral walls of medulla to move laterally (like pages of an open book)
As a result, its roofplate is stretched and greatly thinned
Cavity of this part (future fourth ventricle) becomes somewhat rhomboidal (diamond-shaped)
As walls of medulla move laterally
alar plates come to lie lateral to basal plates
As positions of plates change, motor nuclei generally develop medial to sensory nuclei
Alar plates are lateral to basal plates
Dorsal aspect is open = inferior part of the 4th ventrical

43. Neuroblasts in Basal Plates of Medulla
Develop into motor neurons
Form nuclei (groups of nerve cells) and organize into three cell columns on each side, from medial to lateral:
General somatic efferent (GSE) column:
represented by neurons of hypoglossal nerve that supply tongue muscle
Special visceral efferent (SVE) column:
represented by neurons innervating striated muscles derived from pharyngeal arches (CN V, VII)
General visceral efferent (GVE) column:
represented by some vagus and glossopharyngeal neurons that supply involuntary muscles of respiratory tract, intestinal tract and heart
GSE – CN XII
SVE – CN V, VII
GVE – CN IX, X

44. Neuroblasts in Alar Plates of Medulla
Form neurons arranged in four columns (on each side), from medial to lateral:
General visceral afferent (GVA) column, receiving impulses from gastrointestinal tract and heart
Special visceral afferent (SVA) column, receiving taste buds of tongue
General somatic afferent (GSA) column, receiving impulses from surface of head
Special somatic afferent (SSA), receiving impulses from ear
Choroid plexus  made up of epymendal cells and pia matter
Project here at the bottom of the medulla  makes CSF  3 openings (one middle, two laterally) where CSF goes from the ventricular system to subarachnoid space  granulations in the subarachnoid space return CSF back to cerebral system by way of dural venus sinuses
Column means it can go up into the pons
GSA – CN V (know)
SSA – CN VIII

45. Some Neuroblasts From Alar Plates of Medulla
Migrate ventrally and form:
neurons in the olivary nuclei
Connections with cerebellum and involved in control of movement

46. Metencephalon Walls of metencephalon form:
pons
cerebellum
Cavity of metencephalon forms:
superior part of fourth ventricle
As in rostral part of myelencephalon, pontine flexure causes:
divergence of lateral walls of pons that spreads gray matter in floor of fourth ventricle
Metencephalon
The upper part of the 4th ventricle is located behind the pons
Out growths of the metencephalon will make up the cerebellum  connected to the bonds by 3 cerebellar peduncles (superior, middle, and inferior)
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon (developing pons and cerebellum) showing the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks, respectively, showing successive stages in the development of the pons and cerebellum.

47. Basal Plate Neuroblasts In Metencephalon
Develop into motor nuclei and organize into three columns on each side:
General somatic efferent (GSE) column gives rise to abducens nerve nucleus
Special visceral efferent (SVE) column contains nuclei for trigeminal and facial nerves that innervate first and second pharyngeal arch musculature
General visceral efferent (GVE) column whose axons supply submandibular and sublingual glands
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon (developing pons and cerebellum) showing the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks, respectively, showing successive stages in the development of the pons and cerebellum.
SO4LR6 – superior oblique (CNIV Trochlear, come from the back and comes around), lateral rectus (CNVI – abducens)
GVE – parasympathetic fibers ganglia (also will be involuntary)

48. Alar Plate Neuroblasts In Metencephalon
Develop into sensory nuclei and organize into four columns on each side:
General visceral afferent (GVA) column contains neurons from CN VII (sensation from viscera)
Special visceral afferent (SVA) column contains taste fibers from CN VII
General somatic afferent (GSA) column contains neurons of trigeminal nerve (skin…touch, pressure, temperature)
Special somatic afferent (SSA) column contains neurons from CN VIII (hearing and balance)
Cells from alar plates also give rise to pontine nuclei:
Consist of cerebellar relay nuclei
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon (developing pons and cerebellum) showing the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks, respectively, showing successive stages in the development of the pons and cerebellum.
Ponteine nuclei  give rise cerebellum by superior, middle, and inferior peduncles

49. Metencephalon: Cerebellum
Develops from thickenings of dorsal parts of alar plates called cerebellar swellings (rhombic lips):
project into fourth ventricle
Cerebellar swellings enlarge and fuse in median plane:
overgrow rostral half of fourth ventricle
overlap pons and medulla
Some neuroblasts in the intermediate zone of alar plates migrate to marginal zone and differentiate into:
neurons of the cerebellar cortex
Other neuroblasts from alar plates give rise to:
central nuclei, the largest of which is:
dentate nucleus
The important things to know for this slide (skip nuclei stuff):
Cerebellum is associated posteriorly with the ponds and medulla
- Developed from thickenings of the dorsal part of the alar plate (sensory) = cerebellar swelling

50. Cerebellum Structure Reflects Its Phylogenetic (Evolutionary) Development (slide 1 of 2)
Archicerebellum (flocculonodular lobe) is oldest part phylogenetically
has connections with vestibular apparatus

51. Cerebellum Structure Reflects Its Phylogenetic (Evolutionary) Development (slide 2 of 2)
Paleocerebellum (vermis and anterior lobe) is of more recent development
associated with sensory data from limbs
Neocerebellum (posterior lobe) is newest part phylogenetically
concerned with selective control of limb movements

52. Metencephalon
Nerve fibers connecting cerebral and cerebellar cortices with spinal cord pass through:
marginal layer of ventral region of metencephalon called pons (L. bridge)
contains a band of nerve fibers that crosses median plane
forms a bulky ridge on its anterior and lateral aspects

53. Tela Choroidea and Choroid Plexuses
Thin ependymal roof of fourth ventricle is covered externally by
pia mater
derived from mesenchyme associated with hindbrain
Vascular membrane (pia and associated blood vessels) and ependymal roof form:
tela choroidea (L., web + cord) of fourth ventricle
Because of active proliferation of pia mater, tela choroidea invaginates fourth ventricle and differentiates into:
choroid plexus that produces cerebrospinal fluid (CSF)
Similar plexuses develop in:
roof of third ventricle
medial walls of the lateral ventricles

54. Thin Roof of Fourth Ventricle
Evaginates into outpocketings that rupture in three locations (openings):
One median aperture (foramen of Magendie)
Two lateral apertures (foramina of Luschka)
Openings permit CSF to enter subarachnoid space from fourth ventricle

55. Absorption of CSF into Venous System
Main site is through arachnoid villi
protrusions of arachnoid mater into dural venous sinuses
large venous channels between layers of dura mater
Arachnoid villi consist of:
thin, cellular layer derived from epithelium of arachnoid
endothelium of the sinus

56. CSF Circulation Animation

57. Midbrain (mesencephalon)
Undergoes less change than any other part of developing brain
except for caudal part of hindbrain
Neural canal narrows and becomes:
cerebral aqueduct:
channel that connects third and fourth ventricles
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.

58. Neuroblasts From Alar Plates of Midbrain
Migrate into tectum (L., roof) and aggregate to form:
four large groups of neurons (corpora quadrigemina):
paired superior colliculi (concerned with visual reflexes)
paired inferior colliculi (concerned with auditory reflexes)
Sensory of midbrain
Tectum = roof of midbrain
A, Sketch of the developing brain at the end of the fifth week.
B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates.
C, Sketch of the developing brain at 11 weeks.
D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.

59. Neuroblasts From Basal Plates of Midbrain
Give rise to groups of neurons in the tegmentum (L., covering structure) of midbrain:
red nuclei gives rise to rubrospinal tract (control over tone of limb flexor muscles)
nuclei of third and fourth cranial nerves
reticular nuclei central region of brainstem, occupying most of tegmentum of midbrain, pons, and medulla:
involved in virtually every activity from visceral functions to consciousness
core integrating structure of the brain
Substantia nigra, a broad layer of gray matter adjacent to cerebral peduncle:
associated with functions of basal ganglia:
associated with regulation of motor functions
some authorities believe it is derived from alar plate cells in basal plate that migrate ventrally
Mesencephalic tegmentum is major part of substance of mesencephalon or midbrain that extends from substantia nigra to the level of the cerebral aqueduct.
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.

60. Cerebral Peduncles Of Midbrain
Fibers growing from cerebrum form stemlike cerebral peduncles (crus cerebri) anteriorly
become progressively more prominent as more descending fiber groups pass through on their way to brainstem and spinal cord
Corticopontine
Corticobulbar
Corticospinal (pyramidal)
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.

61. Forebrain Parts
Rostral or anterior part, including primordia of cerebral hemispheres, is telencephalon
Caudal or posterior part of forebrain is diencephalon
Cavities of telencephalon and diencephalon contribute to:
formation of lateral ventricles third ventricle, respectively
A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain showing the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. CN, cranial nerve.
A, Sketch of the dorsal surface of the forebrain indicating how the ependymal roof of the diencephalon is carried out to the dorsomedial surface of the cerebral hemispheres. B, Diagrammatic section of the forebrain showing how the developing cerebral hemispheres grow from the lateral walls of the forebrain and expand in all directions until they cover the diencephalon. The arrows indicate some directions in which the hemispheres expand. The rostral wall of the forebrain, the lamina terminalis, is very thin. C, Sketch of the forebrain showing how the ependymal roof is finally carried into the temporal lobes as a result of the C-shaped growth pattern of the cerebral hemispheres.

62. Telencephalon
Arise at beginning of fifth week as bilateral evaginations of lateral wall of prosencephalon
Consists of two lateral outpocketings called cerebral or telencephalic vesicles:
primordia of cerebral hemispheres and their cavities (lateral ventricles)
A, Schematic lateral view of an embryo of approximately 28 days showing the three primary brain vesicles: forebrain, midbrain, and hindbrain. Two flexures demarcate the primary divisions of the brain. B, Transverse section of this embryo showing the neural tube that will develop into the spinal cord in this region. The spinal ganglia derived from the neural crest are also shown. C, Schematic lateral view of the central nervous system of a 6-week embryo showing the secondary brain vesicles and pontine flexure. The flexure occurs as the brain grows rapidly.

63. Walls of Developing Cerebral Hemispheres
Initially show three typical zones of neural tube:
Ventricular
Intermediate
Marginal
Later a fourth one appears, subventricular zone
Intermediate zone cells migrate into marginal zone and give rise to:
cortical layers
Gray matter is thus located peripherally
axons from its cell bodies pass centrally to form:
large volume of white matter, medullary center
Ventricular – closest to ventricles
Intermediate – aka mantal zone
Marginal
Know gray = outer, and white = inner for cerebral hemispheres

64. Cerebral Hemispheres
Dorsal surface of forebrain, indicating how ependymal roof of diencephalon is carried out to cerebral hemispheres
Developing cerebral hemispheres grow from lateral walls of forebrain and expand in all directions until they cover diencephalon
arrows indicate some directions hemispheres expand
rostral wall of forebrain, lamina terminalis, is very thin
Ependymal roof is carried into temporal lobes as a result of C-shaped growth of cerebral hemispheres
Cavities of cerebral hemispheres are called lateral ventricles:
communicate with lumen of diencephalon through interventricular foramina (of Monro)
Communication between the lateral and the third ventricles  choroid plexus, CSF flows from lateral  third and down into the spinal cord to subarachnoid space
Connection between the lateral and the third ventricles = interventricular foramina

65. Surface of Cerebral Hemispheres
Initially, smooth
As growth proceeds, the following develop:
gyri are rounded surface elevations
sulci are grooves or furrows between gyri
Sulci and gyri permit a considerable increase in surface area of cerebral cortex without requiring an extensive increase in cranial size
Sketches of lateral views of the left cerebral hemisphere, diencephalon, and brainstem showing successive stages in the development of the sulci and gyri in the cerebral cortex. Note the gradual narrowing of the lateral sulcus and burying of the insula (Latin, island), an area of cerebral cortex that is concealed from surface view. Note that the surface of the cerebral hemispheres grows rapidly during the fetal period, forming many gyri (convolutions), which are separated by many sulci (grooves). A, At 14 weeks. B, At 26 weeks. C, At 30 weeks. D, At 38 weeks. E, Magnetic resonance image (MRI) of a pregnant woman showing a mature fetus. Observe the brain and spinal cord. Inset, The smooth lateral (top) and medial (bottom) surfaces of a human fetal brain (14 weeks).

66. Cerebral Growth
Floor of each hemisphere expands more slowly than its thin cortical walls
consequently, cerebral hemispheres become C-shaped
Growth and curvature of hemispheres also affect shape of lateral ventricles
become roughly C-shaped cavities filled with CSF
Caudal end of each cerebral hemisphere turns ventrally and then rostrally, forming temporal lobe
carries lateral ventricle (forming its temporal horn) fissure with it
medial surface, developing right cerebral hemisphere, 13 weeks
21 weeks
Schematic diagrams of the medial surface of the developing right cerebral hemisphere showing the development of the lateral ventricle, choroid fissure, and corpus striatum. A, At 13 weeks. B, At 21 weeks. C, At 32 weeks.
32 weeks

67. As Each Cerebral Hemisphere Grows…
Cortex covering external surface of corpus striatum grows relatively slowly and is soon overgrown
This buried cortex is hidden from view in the lateral sulcus (fissure) of cerebral hemisphere:
Insula (L. island), component of gustatory and olfactory pathways
Sketches of lateral views of the left cerebral hemisphere, diencephalon, and brainstem showing successive stages in the development of the sulci and gyri in the cerebral cortex. Note the gradual narrowing of the lateral sulcus and burying of the insula (Latin, island), an area of cerebral cortex that is concealed from surface view. Note that the surface of the cerebral hemispheres grows rapidly during the fetal period, forming many gyri (convolutions), which are separated by many sulci (grooves). A, At 14 weeks. B, At 26 weeks. C, At 30 weeks. D, At 38 weeks. E, Magnetic resonance image (MRI) of a pregnant woman showing a mature fetus. Observe the brain and spinal cord. Inset, The smooth lateral (top) and medial (bottom) surfaces of a human fetal brain (14 weeks).

68. Insula

69. Cerebral Hemispheres
By middle of second month, basal part of hemispheres bulge into lumen of lateral ventricle and floor of interventricular foramen
Has a striated appearance in transverse sections and is known as corpus striatum

70. Corpus Striatum
As cerebral cortex differentiates, fibers passing to and from it pass through corpus striatum and divide it into:
Dorsomedial portion, caudate nucleus
Ventrolateral portion, lentiform nucleus
Fiber pathway dividing corpus striatum is called internal capsule

71. Caudate Nucleus
Becomes elongated and C-shaped, conforming to outline of lateral ventricle
Its pear-shaped head and elongated body lie in floor of frontal horn and body of lateral ventricle
Its tail makes a U-shaped turn to gain the roof of the temporal or inferior horn of lateral ventricle

72. Region Where Wall of Hemisphere is Attached to Diencephalon Roof
Remains thin, consisting of:
Single layer of ependymal cells covered by vascular mesenchyme
Forms choroid plexus
Disproportionate growth of various parts of hemisphere cause
choroid plexus to protrude into lateral ventricle

73. Diencephalon
Three swellings develop in lateral walls of third ventricle and later become:
Thalamus
Hypothalamus
Epithalamus
Thalamus is separated from epithalamus and hypothalamus by:
epithalamic sulcus
hypothalamic sulcus
not a continuation of sulcus limitans into forebrain
does not divide sensory and motor areas
4th part of diencephalon not shown here – subthalamus
Know that third ventricle separates the two diencephalon
Thalamus = biggest part of the diencephalon
A, External view of the brain at the end of the fifth week.
B, Similar view at 7 weeks.
C, Median section of this brain showing the medial surface of the forebrain and midbrain. D, Similar section at 8 weeks. E, Transverse section of the diencephalon showing the epithalamus dorsally, the thalamus laterally, and the hypothalamus ventrally.

74. Thalamus Develops rapidly on each side
Bulges into cavity of third ventricle, reducing it to a narrow cleft
Thalami meet and fuse in the midline in approximately 70% of brains
forming a bridge of gray matter across the third ventricle, interthalamic adhesion
Consists of numerous nuclei that have extensive reciprocal connections with cerebral cortex
Thalamus

75. Arises by proliferation of neuroblasts in intermediate zone of diencephalic walls, ventral to hypothalamic sulci
Later, a number of nuclei concerned with endocrine activities and homeostasis develop
A pair of nuclei, mammillary bodies, form pea-sized swellings on ventral surface of hypothalamus
Hypothalamus

76. Epithalamus
Develops from roof and dorsal portion of lateral wall of diencephalon
Initially, epithalamic swellings are large
later they become relatively small
Pineal gland (pineal body) develops as a median diverticulum of the caudal part of roof of diencephalon
Proliferation of cells in its walls converts it into a solid cone-shaped gland
Produces melatonin

77. Pituitary Gland (L., Hypophysis)
Ectodermal in origin
Develops from two sources:
Upgrowth from ectodermal roof of stomodeum, hypophysial diverticulum (Rathke's pouch)
Downgrowth from neuroectoderm of diencephalon, neuro-hypophysial diverticulum

78. Cerebral Commissures
As cerebral cortex develops, groups of nerve fibers connect corresponding areas of cerebral hemispheres with one another (commissures)
Most important cross in the lamina terminalis:
rostral (anterior) end of forebrain
extends from roof plate of diencephalon to optic chiasm (decussation of optic nerve fibers)
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

79. First Commissures to Form…
Anterior commissure and hippocampal commissure:
small fiber bundles that connect phylogenetically older parts of brain
Anterior commissure connects:
olfactory bulb and related areas of one hemisphere with those of opposite side
Hippocampal commissure connects:
hippocampal formations, involved with learning and memory
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

80. Anterior Commissure
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

81. Hippocampal Commissure
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

82. Largest Cerebral Commissure: Corpus Callosum
Connects cortical hemispheres
Initially lies in lamina terminalis
Fibers are added to it as cortex enlarges
as a result, it gradually extends beyond lamina terminalis
Rest of lamina terminalis lies between corpus callosum and fornix (hippocampus fiber bundle)
becomes stretched to form thin septum pellucidum, a thin plate of brain tissue
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

83. Corpus Callosum
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.

84. Septum Pellucidum
A, Drawing of the medial surface of the forebrain of a 10-week embryo showing the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina showing the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks showing division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated.