1. Introduction to Developmental Biology
January 12, 2009

2. The following slides….
This material is intended to show you the level of knowledge that you will need master for any given topic
It is NOT what you should already know, but you should have the background enabling you to learn this material
We will go over material from Gilbert and from other sources when additional information is needed for illustration and clarity

3. An Introduction to Embryonic Development
Developmental processes include
Gamete formation, fertilization
Embryogenesis
Metamorphosis
Sexual maturation
Wound healing
Tissue, organ regeneration
Stem cell behavior
Many cancers

4. What regulates development?
Developmental programs
Internally programmed
Induced
Cell-Cell interactions
Junctions and adhesion molecules
Signaling through secreted factors or membrane-tethered molecules
Cell-Extracellular matrix interactions
Integrins and adhesive specializations
Cell and tissue reorganization
Epithelial-Mesenchymal Transformation (and/or back)

5. An Example of material covered
Epithelial/Mesenchymal Transformation
Rearranging cells and tissues to build structures and organs
Epithelial Mesenchymal Interactions
Changing the differentiated state of cells and tissue through an exchange of signals between adjacent tissues

6. Epithelial-mesenchymal Interactions
Chapter 6, 15 Gilbert
Progressive interactions of tissues through cell-cell interactions mediated by:
Direct contact
CAMS
Cadherins
Junctions
Notch/delta type interactions
ECM
Matrix to matrix
Integrins
Secreted growth factors
Shh
Wnt
FGFs
TGF-βs
BMPs
Specific receptors

8. -Apical/Basal Polarity
Basal Lamina
Epithelia: Cell sheets, tubes or cords of cells with basal lamina and subapical junctional complexes
-Apical/Basal Polarity
Basal Lamina
E.D. Hay
You will need to understand the relationship between organelle structure and cell/tissue function

9. Integrin binding induces formation of a focal adhesion
Inter. Fil.
actin
Integrin binding induces formation of a focal adhesion
Focal adhesions bind actin filaments. The focal adhesions are joined by hemidesmosomes, which associate with intermediate filaments

10. Receptor tyrosine kinase activity
Ras and Growth Factors
You will need to learn and understand signaling pathways
Receptor tyrosine kinase activity

11. You will need to be able to learn and understand structure and function of ECM

12. Binds the Integrin
Fibronectin: two 220 kDa chains, multiple binding domains.

13. You will need to apply these facts, functions and mechanisms to synthesize an understanding of increasingly complex systems as the semester goes on.

14. Induction and response
There are inducing tissues that produce a signal and
Responding tissues that make some change in response to the signal
In order to respond a tissue must be competent
State of differentiation
Presence of receptors
Mutual interactions can occur simultaneously (limb, kidney) or sequentially (teeth)

15. Instructive vs Permissive
If a signal from one cell/tissue is required for the response of a target cell/tissue, that is called an Instructive Interaction
If a tissue has all of the factors it needs to develop/differentiate within itself and only needs an enviornment that allows intrinsic processes to occur, that is called a Permissive Interaction

16. Some interactions are epithelial/epithelial, some epithelial/mesenchymal

17. Example of instructive interaction: epithelial/epithelial

18. Progressive interactions in eye development
Shows interaction between the optic vesicle and the lens placode to induce lens formation. Then an interaction between lens and prospective retina affecting neural retinal development. --Mutual interaction

19. But the optic vesicle/lens placode interaction is not the start of the inductive cascade….

20. Lens induction in newts

21. Progressive interactions in lens induction
Inducers have additive effect
Order of tissues with inductive capacity:
Pharyngeal endoderm
Cardiac mesoderm
Optic vesicle
The lens epithelium must be competent to respond
-role of Pax6:
-Pax 6 expression occurs if the early inductive interactions have occurred
-as long as the lens/surface ectoderm can express Pax 6, then the lens can form

22. You will need to learn about patterning genes
Competence and lens induction: role of Pax6

23. Progressive interactions in eye development
Must be Pax6 positive

25. Feather formation: epithelial/mesenchymal between the skin ectoderm and dermis

26. Classical Example of Epithelial/Mesenchymal Interaction

27. Feather germ formation and development
• The epidermis makes the skin appendage (feather, etc), but the type of appendage made is determined by instructions from the dermis in different regions of the body
If epidermis from the wing is paired with dermis from the leg, scales will form instead of feathers
Studying feather and scale formation in chick in detail shows a more complicated explanation and a potential role of the epidermis.
Combining feather-region epidermis with 13-day chick embryo tarsometatarsal dermis forms scales.
However, when recombined the same epidermis with a 10-day tarsometatarsal dermis it forms feathers.
This means that the dermis acquires it inductive ability gradually and the epidermis has an inherent identity that can be overcome by competent dermis
FGF3 and 10 are produced by the dermis in the area where a feather will be induced

28. Mouse feathers
It is possible to combine chick skin epidermis that will form feathers with pre-instructive dermis from mouse and the mouse dermis will “go along” with the program of the skin to make mouse feathers (Dhouailly)

29. Overall Goal of K331
We will learn about processes and mechanisms used in the formation and development of many tissues and organs
We will examine the formation of embryonic germ layers, tissues and organs, giving you a basic foundation in Developmental Biology
But NOT all of the organs in the body
By studying a range of tissues and organs you will develop the tools to study any tissue or organ development