1. Cell-cell Communications in Development

2. Induction and Competence
What do we mean by induction?
How do we
define
competence?
Where does Pax6
fit in?
Induction – influence of one group of cells on adjacent cells
Competence – able to respond to inducer
Pax6 is a competence factor – needed by responder

3. Induction and Competence
Where can we observe reciprocal inductions?
Formation of eye in mouse

4. Induction and Competence
What is the difference between instructive and permissive interactions?
Instructive – inducing cell provides needed information to responder
Permissive –all information is present in responder, requires a favorable environment

5. Epithelial-mesenchymal interactions
Nature of epidermal structure depends upon from where mesenchyme comes
How does this diagram illustrate the regional specificity of induction?

6. Epithelial-mesenchymal interactions
Responder’s genome dictates structures that will form
How does this experiment illustrate the genetic specificity of induction?

7. Paracrine Factors in Development
What is the connection between paracrine factors and induction?

8. Paracrine Factors in Development
How do fibroblast growth factors (FGF’s) induce changes in cells?
Leads to phosphorylation and activation of cell protein
About 24 different genes producing FGF’s are known

9. Paracrine Factors in Development
What is the Hedgehog family?
Family of genes acting as paracrine factors – induce particular tissues or tissue boundaries
In vertebrates, sonic hedgehog, desert hedgehog, indian hedgehog
Picture show active sonic hedgehog gene

10. Paracrine Factors in Development
The wnt family?
Family of proteins involved in induction of urogenital development among other things

11. Paracrine Factors in Development
The TGF-β superfamily?
BMP’s within TGF are involved in inducing bone formation; TGF are involved in formation of extracellular matrix and in regulating cell division

12. Signal Transduction Pathways
What is involved in signal transduction?
Transmembrane protein; extracellular receptor binds ligand; induces conformational change in receptor; changes cyctoplasmic domain; activates enzyme; alters intracellular protein

13. Signal Transduction Pathways
How does the RTK pathway promote cell-cell induction?
Leads to activation of trascription factor in nucleus

14. Signal Transduction Pathways
What are examples of some specific inductions that use the RTK pathway?
Induction of photoreceptors in Drosophilia
Induction of vulva in C. elegans
Induction of melanin forming pathway in pigment cells of retinia; related to activation of Mitf transcription factor

15. Signal Transduction Pathways
How does the Smad pathway compare with the RTK pathway?
Different ligands; heterodimeric receptor; autophosphorylation;phosphorylated intermediates; activation of transcription factors

16. Signal Transduction Pathways
What pathway mediates both the differentiation of blood cells and the formation of milk for lactation?
JAK-STAT; also important in human fetal bone growth

17. Signal Transduction Pathways
How can the Wnt pathway mediate cell division?
What are the ramifications of this pathway?
B-catenin causes activation of cell division genes such as c-myc

18. Signal Transduction Pathways
How does the sonic hedgehog paracrine factor influence limb and neural development in vertebrates?
Mutants of sonic hedgehog can lead to limb abnormalities and single eye formations

19. Signal Transduction Pathways
What happens in the absence of sonic hedgehog?
How is cholesterol involved here?

20. Cell Death Pathways
What is the difference between apoptosis and necrosis?
Why is apoptosis critical for development?
What initiates apoptosis?
apoptosis – programmed cell death; necrosis – cell death due to disease or infection
needed for digit formation, spacing of neurons, generating middle ear, etc.
signal molecules like BMP4 in teeth

21. Cell Death Pathways
What role has C. elegans played in our knowledge of apoptosis?
Brenner, Horvitz, Sulston – Nobel prize in 2002
CED-9 can bind to and inactivate CED-4
CED-4 protease activating factor; CED-3 protease
in mammals – proteases caspase 9 and 3 are similar to CED-3 and Apaf1 is homologue of CED-4 and Bcl2 is similar to CED-9

22. Juxtacrine Signaling
How is this type of signaling different from paracrine signaling?
signal molecule is a protein that resides in adjacent cell member
generally doesn’t involve a diffusable signal molecule

23. Juxtacrine Signaling
Notch proteins are important receptors in neuron development

24. Juxtacrine Signaling
Ligand resides in extracellular matrix of signaling cell
fibronectin
laminin
What kinds of receptors are involved?
integrins – bind to arginine-glycine-aspartate extracellularly and intracellularly bind to α-actinin and talin
matrix has been shown to induce specific gene expression in liver, testis and mammary gland

25. Juxtacrine Signaling
Gene activation by matrix attachment

26. Juxtacrine Signaling
signal transmitted from cytoplasm of one cell directly to cytoplasm of second cell
use gap junction
antibodies to connexins cause vary forms of abnormal development

27. Pathway’s Cross Talk
transcription may require activation of two pathways
one receptor can activate different pathways
differentiation of T lymphocyte
FGF can activate RTK or STAT pathwys

28. Maintaining Differentiation
Transcription factor as its own enhancer
MyoD factor in muscle cells

29. Maintaining Differentiation
Prevent nucleosome formation

30. Maintaining Differentiation
Autocrine stimulation
Sertoli cells of testis

31. Maintaining Differentiation
Paracrine loop
vertebrate limb