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| Qualifications |
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1984 B.S. Paul Sabatier University, Toulouse, France, Developmental Biology |
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| Research Interests |
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Control of neural crest development in Xenopus.
The neural crest is a unique embryonic structure composed of a migratory population of multipotent cells arising at the lateral edges of the neural plate, junction between the neural and the non-neural ectoderm. During neurulation, neural crest becomes positioned at the dorsal most aspect of the neural tube. As the neuroepithelium closes, neural crest cells delaminate in a rostro-caudal wave and migrate throughout the embryo along specific and restricted routes. Once they reach their final destination neural crest cells will differentiate in a large variety of cell types including neurons and glial cells of the peripheral nervous system, craniofacial cartilage and bone, smooth muscle and pigment cells. Defining the molecular basis of neural crest specification and diversity is of major importance to understand diseases arising from aberrant neural crest development.
My laboratory is interested in defining the molecular processes involved in the specification and diversification of the neural crest cells during Xenopus laevis development.
Sox proteins fall into a large class of transcription factors related to SRY, the testis-determining factor. They are characterized by the presence of an HMG-box, a sequence specific DNA binding domain. Expression of these proteins in defined cell types during embryogenesis appears to govern cell fate determination.
We have recently isolated two members of this family, Sox9 and Sox10, and analyzed their function during Xenopus development. Sox9 and Sox10 accumulate shortly after gastrulation at the lateral edges of the neural plate, in the neural crest-forming region. In this tissue, they both co-localize with Slug, one of the earliest genes activated in response to neural crest-inducing signals.
As development proceeds, Sox9 and Sox10 exhibit a complementary expression pattern. While Sox9 persists primarily in migrating cranial neural crest cells as they populate the pharyngeal arches, Sox10 expression is down regulated in the cranial region and persists mostly in late migrating neural crest cells in the trunk.
Depletion of Sox9 protein in developing embryos, using morpholino antisense oligos (Sox9-AS), causes a dramatic loss of neural crest progenitors (Slug) and an expansion of the neural plate. Later during embryogenesis, morpholino-treated embryos have a specific loss or reduction of neural crest-derived craniofacial skeletal elements.
Overexpression of Sox10 at the gastrula stage, using a hormone inducible construct, leads to ectopic formation of neural crest progenitors (Slug). By the tailbud stage, Sox10-injected embryos present a massive increase of pigment cells, one major derivative of the trunk/vagal neural crest.
There is a remarkable parallel between the activity of Sox9 in the cranial neural crest and Sox10 function in the trunk/vagal neural crest, suggesting that during embryogenesis a limited number of Sox proteins, differentially expressed in the developing neural crest, are required for the specification and differentiation of subsets of neural crest derivatives as they emerge at different axial levels.
Current research projects:
-Timing of Sox9 and Sox10 requirement for neural crest formation.
Other research interests include control of inner ear formation by Sox family members: |
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| Selected Publications |
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He X., Saint-Jeannet J.-P., Woodgett J., Varmus H. E. and Dawid I. B. (1995). Glycogen synthase kinase 3 and dorsoventral patterning in Xenopus embryos. Nature 374, 617-622.
Taira M., Saint-Jeannet J.-P., and Dawid I. B. (1997). Role of Xlim-1 and Xbra genes in anteroposterior patterning of the neural tissue by the head and trunk organizer. Proc. Natl. Acad. Sci. (USA) 94, 895-900.
He X., Saint-Jeannet J.-P., Wang Y., Nathans J., Dawid I. B and Varmus H. E. (1997). A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 275, 1652-1654.
Spokony R. F. and Saint-Jeannet J.-P. (2000). Xenopus FK 506-binding protein, a novel immunophilin expressed during early development. Mech. Dev. 94, 205-208.
Tamai K., Semenov M., Kato Y., Spokony R. F., Liu C., Katsuyama Y., Hess F., Saint-Jeannet J.-P. and He X. (2000). LDL receptor-related proteins in Wnt signal transduction. Nature 407, 530-535.
Deardorff M. A., Tan C., Saint-Jeannet J.-P. and Klein P. S. (2001). A role for frizzled-3 in neural crest development. Development 128, 3655-3663.
Tan C., Deardorff M. A., Saint-Jeannet J.-P., Yang J., Arzoumanian A. and Klein P. S. (2001). Kermit, a frizzled interacting protein, regulates frizzled-3 signaling in neural crest development. Development 128, 3665-3674.
Spokony R. F., Aoki Y., Saint-Germain, N., Magner-Fink, E. K., and Saint-Jeannet J.-P. (2002). The transcription factor Sox9 is required for cranial neural crest development in Xenopus. Development 129, 421-432.
Wu J., Saint-Jeannet J.-P. and Klein P. S. (2003). Wnt-frizzled signaling in neural crest formation. Trends Neurosci. 26, 40-45.
Luo T., Lee Y-H., Saint-Jeannet J.-P. and Sargent T. D. (2003). Induction of neural crest in Xenopus by transcription factor AP2?. Proc. Natl. Acad. Sci. (USA) 100, 532-537.
Wang Y., Saint-Jeannet J.-P. and Klein P. S. (2003). Wnt-frizzled signaling in the induction and differentiation of the neural crest. BioEssays 25, in press.
Aoki Y., Saint-Germain N., Gyda M., Magner-Fink E. K., Lee Y-H., Credidio C. and Saint-Jeannet J.-P. (2003). Sox10 regulates the development of the neural crest-derived melanocytes in Xenopus. Submitted.
Current Laboratory Personnel:
Christine Credidio : Research Specialist credidio@mail.vet.upenn.edu
(from left to right: Young-Hoon lee, Christine Credidio, Michael O’Donnell and Xiao Huang) |
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