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Jean-Pierre
Saint-Jeannet
Associate
Professor, Dept of Animal Biology, School of Veterinary Medicine
and Cell & Devevelopmental Biology
Developmental
Biology Program
Address
Old Vet Bldg, Room 195E
3800 Spruce Street
Philadelphia, PA 19104-6046
Office tel.: 215 898-1666
Lab tel.: 215 898-1667
Fax: 215 573-5186
E-mail: saintj@vet.upenn.edu
Link(s)
Dr.
Saint-Jeannet at the Vet School
Education
Universite Paul Sabatier,
B.S. (Developmental Biology), 1984
Universite Paul Sabatier, M.S. (Neuroscience), 1986
Universite Paul Sabatier, Ph.D. (Developmental Neurobiology),
1990
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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.
Search PubMed for articles
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.
Recent
Publications
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.
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. Dev. Biol. 259, 19-33.
Saint-Germain N., Lee Y-H., Zhang, Y., Sargent
T. D. and Saint-Jeannet J-P. (2004). Specification of the
otic placode depends on Sox9 function in Xenopus. Development
131, 1755-1763.
Lee Y-H., Aoki Y., Hong C-S., Saint-Germain
N., Credidio, C. and Saint-Jeannet J-P. (2004). Early requirement
of the transcriptional activator Sox9 for neural crest induction
in Xenopus. Dev. Biol. 275, 93- 103.
Huang X., Hong C-S., O'Donnell M. and Saint-Jeannet
J-P. (2005). The doublesex-related gene, XDmrt4, is required
for neurogenesis in the olfactory system. Proc. Natl.
Acad. Sci. (USA). In press.
Lab
Rotation
Projects
- Profiling the transcriptome of individual neural crest
progenitors
- Analysis of Sox8 and Sox10 function during otic placode
specification and patterning
- Identification and analysis of Sox8, Sox9 and Sox10 target
genes during neural crest and otic placode formation
- Identification and analysis of XDmrt4 target genes in
the olfactory placode/epithelium
- 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
last updated 6/2005
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