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Cell-Cell
Signaling during Vertebrate Development 
The molecular and biochemical characterization of major signaling pathways
Two important unsolved questions in Hh signaling are (1) the molecular
mechanisms by which Hh protein exerts long-range signaling activity over
a distance of tens of cell diameters and in this process induces distinct
cell fates in a dose-dependent manner and (2) the biochemical mechanism
of signal transduction. To fully understand this process requires the
identification of all the key players. We have identified and characterized
a new component, Hip (Hedgehog-interacting protein), of the Hh pathway.
We are in the process of identifying additional components and testing
models of Hh signal transduction.
Lung branching morphogenesis as a model system to study signal integration
during vertebrate embryogenesis
A major challenge in studying signaling pathways is to understand how
all of the signals are integrated to make a tissue or organ. This would
require a mechanistic description of cell proliferation, migration, determination
and cell death in three dimensions and in real time. We have chosen lung
branching in mice as a model system. Our goal is to identify genes involved
in setting up the initial branching pattern of the lung epithelium and
understand their molecular mechanisms.
Gene trapping to identify genes essential for cardiopulmonary development
and diseases
We are involved in the NHLBI-Bay Area Functional Genomics Consortium (http://baygenomics.ucsf.edu/)
which uses custom gene-trap vectors to inactivate thousands of genes in
mouse embryonic stem (ES) cells. Through a combination of computational
approaches, expression profiling with DNA microarrays, and in situ hybridization,
we hope to identify trapped lines that are likely to be valuable for understanding
cardiopulmonary development and diseases. Knockout mice generated from
these trapped lines will provide significant insights into the molecular
mechanisms of cardiopulmonary development and diseases.
Selected Publications:
McMahon A.P.; Chuang P.-T. 1996. Hedgehogs in the clinic. Nature Medicine
2:1308-1310.
Yang Y.; Drossopoulou G.; Chuang P.-T.; Duprez D.; Marti E.; Bumcrot D.;
Vargesson N.; Clarke J.; Niswander L.; McMahon A.; Tickle C. 1997. Relationship
between dose, distance and time in Sonic Hedgehog-mediated regulation
of anteroposterior polarity in the chick limb. Development 124: 4393-4404.
Chuang P.-T.; McMahon A.P. 1999. Modulation of vertebrate Hedgehog signaling
through the induction of a Hedgehog-interacting protein. Nature 397: 617-621.
Chuang P.-T.; Kornberg T.B. 2000. On the range of Hedgehog signaling.
Curr. Opin. Genet. Dev. 10: 515-522.
Huo L.; Roessler E.; Dutra A.; Chuang P.-T.; McMahon A.P.; Muenke M. 2000.
Determination of the chromosomal location and genomic structure of the
Hedgehog -Interacting Protein gene and analysis of its role in holoprosencephaly.
Gene Funct. Dis 3-4, 119-127.
Treier M.; OÍConnell S.; Gleiberman A.; Price J.; Szeto D.P.; Burgess
R.; Chuang P.-T.; McMahon A.P.; Rosenfeld M.G. 2001. Hedgehog signaling
is required for pituitary gland development. Development 128: 377-386.
Bonifas J.M.; Pennypacker S.; Chuang P.-T.; McMahon A.P.; Williams M.;
Rosenthal A.; De Sauvage F.J.; Epstein E.H. 2001. Activation of Expression
of Hedgehog Target Genes in Basal Cell Carcinomas. J Invest Dermatol 116:
739-742.
Contact Information:
Email: chuang@cvrimail.ucsf.edu
Phone: 415/ 514-0667
Address: Box 0130, Room HSE 1310
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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