1. How does a single cell make a brain???
Neural Development
How does a single cell make a brain???
How are different brain regions specified??? 1

2. How do cells become neurons? Environmental factors Positional cues
Neural Development
How do cells become neurons?
Environmental factors
Positional cues
Genetic factors
Competence
Cell lineage
Timing 2

3. Neural Development depends on genes and environment
Keywords in Development
Induction: Cells are instructed to adopt a fate by signals in the environment.
Competence: the ability of a cell to respond to a signal. It depends on the receptors, transcription factors, etc expressed by the cell.
Differentiation: Cell elaborates a specific developmental program.
Determination: A cell is restricted in its developmental potential. 3

4. Major Processes in Development
egg
embryo
1n + 1n = 2n
1. Mitosis
-cell division
2. Patterning
-cells are arranged in proper positions
-the body plan is established
3. Differentiation
-cells become different from each other
-they acquire specific functions 4

5. Initial Steps in the Development of the Nervous System:
Fertilization
Cleavage
Gastrulation
Neurulation 5

6. Looking at early development of the nervous system: Xenopus Frog
Cleavage
Gastrulation
Fertilization
Neurulation 6

7. Early events in neural development
Gastrulation :
Gastrulation is the process by which the embryo acquires 3 germ layers. There is intense cell movement and rearrangement
Ectoderm Major tissues of the Nervous System, Epidermis
Mesoderm Connective Tissue, Muscle, Vessels
Endoderm  guts, lungs, liver 7

8. movie 8

9. Early events in neural development
Gastrulation Neurulation 9

10. Neurulation: Formation of the Neural Tube
After Gastrulation comes Neurulation.
During Neurulation, the neural plate invaginates, and the neural folds close to form the neural tube. 10

11. PNS (sensory ganglia, ANS), melanocytes, adrenal medula
Long After Neurulation:
Neural Tube
Neural Crest
Rostral
Caudal
PNS (sensory ganglia, ANS), melanocytes, adrenal medula
Brain
Spinal Cord 11

12. - How do cells become neurons?12

13. Early events in neural development
Gastrulation Neurulation 13

14. Classic experiment showing the induction of the nervous system
Hans Spemann discovered the organizer----Nobel 1935
Expt: Transplant different parts of the
developing embryo (donor)
into another embryo (host)
Result: 1) If the dorsal lip is transplanted,
a second embryonic axis forms
2) The second embryo has
both host and donor tissue
Take the DLB from a pigmented donor and place it on the ventral ectoderm (epidermal future) of a host. The differentiation of the NEURAL PLATE from the uncommitted ectoderm in amphibian embryos depends on signals secreted by a specialized group of cells called the organizer regions. 14

15. 15

16. Model: Inductive signal in dorsal lip instructs ectoderm
The organizer region is responsible for converting ectoderm into neural cells
Model: Inductive signal in dorsal lip instructs ectoderm 16

17. How does the organizer instruct epidermal cells?
Experiment: Dissociate animal cap, grow in culture
Result: Neurons can form in the absence of the organizer
The default is to become neural
Model: Epidermis makes local signal that inhibits neural fate 17

18. How does the organizer instruct epidermal cells?
Experiment:
Inject blastula with genes of interest. Do any cause animal cap to
become neural?
Result:
Expression of a dominant negative mutant
of a BMP receptor results in neural fate.
Model: BMP signal instructs cells not to become neural 18

19. Activation of BMP signaling inhibits the neural fate
NOT NEURAL
BMP signaling: receptor serine kinase 19

20. How does the organizer instruct epidermal cells?
Experiment:
Inject blastocyst with genes from the organizer and see if any cause the animal cap to become neural
Neural fate (?)
Take the animal cap
Inject mRNAs
Noggin is a secreted protein, expressed in the organizer and later in the notocord.
Noggin inhibits BMP signaling.
Follistatin and chordin have similar functions. 20

21. Inhibition of BMP signaling makes cells adopt neural fate
== NOGGIN
NEURAL 21

22. Current Model for how cells become neural
Default state is neural
Local secretion of BMPs by epidermis inhibits neural fate
Local secretion of noggin, chordin by dorsal lip or mesoderm inhibits BMP signaling
Inhibition of BMP signaling give rise to neural fate
Double Inhibition Model for Neural fate 22

23. Model: The ‘double inhibition model’ for neural fate23

24. A cell’s fate will depend on the signals to which it is exposed as well as the developmental history of the cell (which genes they express) 24