Cell & Developmental Biology
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Jean-Pierre Saint-Jeannet, Ph.D.

Associate Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology

Contact information
Old Vet Bldg, Room 195E
3800 Spruce Street
Philadelphia, PA 19104
Office: 215 898-1666
Fax: 215 573-5186
Education:
B.S. (Developmental Biology)
Universite Paul Sabatier, 1984.
M.S. (Neuroscience)
Universite Paul Sabatier, 1986.
Ph.D. (Developmental Neurobiology)
Universite Paul Sabatier, 1990.
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Description of Research Expertise

Research Interests
Control of neural crest and placodes formation in Xenopus

Key words: Xenopus, induction, patterning, neural crest, craniofacial, melanocytes, inner ear, otic placode, olfactory placode, Sox and Dmrt genes.

Description of Research
We are studying the molecular processes involved in the specification of the neural plate border in Xenopus laevis. The neural plate border will give rise to two important cell populations the neural crest and the placodes. More specifically, we are focusing our interest on the Sox and Dmrt families of transcriptional regulators. Sox proteins fall into a large class of transcriptional regulators related to SRY, the testis determining factor. They are characterized by the presence of an HMG-box, a sequence specific DNA binding domain. Genes related to the Drosophila doublesex constitute the Dmrt gene family and have been primarily implicated in sexual development. This class of molecules is characterized by a signature zinc finger-like DNA-binding motif known as the DM domain.

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. 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 includingneurons and glial cells of the peripheral nervous system, craniofacial cartilage and bone, smooth muscle and pigment cells. We have isolated three Sox family members, Sox8, Sox9 and Sox10, that exhibit differential expression pattern within the neural crest and its derivatives. While Sox10 has been implicated in the development of pigment cell, a trunk neural crest derivative, Sox9 appears to control the development of neural crest-derived craniofacial skeletal elements. Thisremarkable parallel between the activity of Sox9 in the cranial neural crest and Sox10 function in the trunk neural crest, suggest that 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.

The inner ear develops from a thickening of the embryonic ectoderm, adjacent to the hindbrain, known as the otic placode. The placode invaginates to form first the otic cup and then the otic vesicle or otocyst. With the exception of the pigment cells of the stria vascularis and the secretory epithelium of the cochlea, which are of neural crest origin, all components of the inner ear derive from the embryonic otic placode. Sox9 is expressed in the presumptive otic placode shortly after gastrulation. Sox9 depletion in developing embryos leads to a severe loss of the early otic placode markers Pax8 and Tbx2 and in the most extreme cases these embryos fail to form an otic vesicle. Using a hormone inducible dominant negative Sox9 construct, we found that Sox9 function is required during gastrulation for otic placode specification but not for its subsequent patterning.

The anterior neural ridge defines a subdomain of the pre-placodal ectoderm at the rostral boundary of the neural plate, and the prospective olfactory placode and some forebrain tissues will develop from this region. In Xenopus, Dmrt4 (XDmrt4) is initially expressed in the anterior neural ridge and then becomes progressively restricted to part of the telencephalon and the olfactory placode/epithelium. Interference with XDmrt4 function by injection of a morpholino oligonucleotide or an inhibitory mutant resulted in a similar phenotype, the specific disruption of the olfactory placode expression of Xebf2 without affecting the expression of other placodal markers. Xebf2 belongs to a family of helix loop-helix transcription factor implicated in neuronal differentiation, and later in embryogenesis XDmrt4 deficient embryos show impaired neurogenesis in the olfactory epithelium. Consistent with this finding, XDmrt4 is sufficient to activate Neurogenin, Xebf2 and N-CAM expression in animal explants and is required for Noggin-mediated neuralization. XDmrt4 is an important regulator of neurogenesis in the olfactory system.

Rotation Projects for 2006-2007
1. Profiling the transcriptome of individual neural crest progenitors
2. Analysis of Sox8 and Sox10 function during otic placode specification and patterning
3. Identification and analysis of Sox8, Sox9 and Sox10 target genes during neural crest and otic placode formation
4. Identification and analysis of XDmrt4 target genes in the olfactory placode/epithelium
5. Characterization of novel Dmrt genes expressed in the pre-placodal ectoderm

Lab personnel:
Christine Credidio, Research Specialist
Chang-Soo Hong, PhD, Postdoctoral Researcher
Diane Raines, Lab Assistant

Selected Publications

Hong C-S., Park B-Y. and Saint-Jeannet J-P. : Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm. Development 135: 3903-3910, 2008.

Park B-Y. and Saint-Jeannet J-P. : Hindbrain-derived Wnt and Fgf signals cooperate to specify the otic placode in Xenopus. Dev. Biol. 324: 108-121, 2008.

Hong C-S. and Saint-Jeannet J-P. : The activity of Pax3 and Zic1 regulates three distinct cell fates at the neural plate border. Mol. Biol. Cell 18: 2192-2202, 2007.

Hong C-S., Park B-Y. and Saint-Jeannet J-P. : The function of Dmrt genes in vertebrate development: it is not just about sex. Dev. Biol. 310: 1-9, 2007.

O’Donnell, M., Hong C-S., Huang X., Delnicki, R. J. and Saint-Jeannet J-P. : Functional analysis of Sox8 during neural crest development in Xenopus. Development 133: 3817-3826, 2006.

Huang X., Hong C-S., O'Donnell M. and Saint-Jeannet J-P.: The doublesex-related gene, XDmrt4, is required for neurogenesis in the olfactory system. Proc. Natl. Acad. Sci. (USA) 102: 11349-11354, 2005.

Hong C-S. and Saint-Jeannet J-P. : Sox proteins and neural crest development. Sem. Cell Dev. Biol. 16: 694-703, 2005.

Saint-Germain N., Lee Y-H., Zhang, Y., Sargent T. D. and Saint-Jeannet J-P.: Specification of the otic placode depends on Sox9 function in Xenopus. Development 131: 1755-1763, 2004.

Huang X. and Saint-Jeannet J-P.: Neural crest induction and the opportunities of life on the edge. Dev. Biol. 275: 1-11, 2004.

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Last updated: 07/11/2011
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Department of Cell and Developmental Biology
1150 BRB II
421 Currie Boulevard
Philadelphia, PA 19104
Tel: (215) 573-9306
Fax: (215) 898-9871