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Jean-Pierre Saint-Jeannet, Ph.D.

Click here for selected publications since Dr. Saint-Jeannet's arrival at Penn

RESEARCH INTERESTS

RESEARCH TECHNIQUES

RESEARCH SUMMARY

In the dorsal portion of the vertebrate neuroepithelium lies the neural crest, a migratory population of cells that have the ability to produce a variety of cell types including autonomic and sensory neurons, cartilage, 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.

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, causes a dramatic loss of neural crest progenitors 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. By the tailbud stage, Sox10-injected embryos present a massive increase of pigment cells, one major derivative of the trunk neural crest.

There is a remarkable parallel between the activity of Sox9 in the cranial neural crest and Sox10 function in the trunk 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.

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The Saint-Jeannet Lab