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Pao-Tien Chuang, MD, PhD
Hedgehog Signaling in Mammalian Embryogenesis and Postnatal Physiology
Selected Publications | Complete Publications
phone
(415) 514-0667
email
pao-tien.chuang@ucsf.edu
additional websites
 Lab Website
Tetrad Graduate Program Cardiovascular Research Institute
secondary
research affiliation
Tissue/Organ Biology & Endocrinology
We study the molecular mechanisms of Hedgehog (Hh) signaling in mammalian development and physiology, using mouse as a model system. The Hh pathway plays a key role in many aspects of embryonic development, and dysregulation of Hh signaling is associated with human congenital anomalies and cancers. A combination of mouse genetics (transgenic and knockout mice), cell biology and biochemistry is utilized to address three major issues:

(1) The molecular characterization of the Hedgehog signaling pathway. We currently investigate how the Hh ligand is produced, lipidated, and transported to generate a morphogen gradient, and the molecular mechanisms by which the Hh signal is transduced. These studies serve as a paradigm for understanding lipid biology and vesicular trafficking in morphogen gradient formation, the involvement of cellular organelles, including the nucleus and the primary/motile cilia in receiving and interpreting the signal, and the evolution of developmental pathways.

(2) The role of Hedgehog signaling in various aspects of postnatal physiology and homeostasis such as stem cell maintenance and cancer formation. The postnatal roles of major signaling pathways remain poorly defined despite the widespread belief that they play a central role in postnatal development, physiology and homeostasis. We are developing tools to address this fundamental question.

(3) Lung branching morphogenesis as a model system to study signal integration during mammalian embryogenesis. A major challenge in studying signaling pathways is to understand how multiple signals are integrated to make a tissue or organ. We have chosen lung branching in mice as a model system for a number of reasons. With the availability of organ culture, the stereotyped branching process and the ease of following the branching process, the lung is an attractive system to address the molecular mechanisms of branching morphogenesis, a process that involves epithelial-mesenchymal interactions and plays an essential role in the formation of many other organs.


Selected Publications
Chuang P.-T., McMahon A.P. 1999. Modulation of vertebrate Hedgehog signaling through the induction of a Hedgehog-binding protein. Nature 397(6720):617-21.

Kawakami T., Kawcak T., Li Y.-J., Zhang W., Hu Y., Chuang P.-T. 2002. Mouse dispatched mutants fail to distribute Hedgehog proteins and are defective in Hedgehog signaling. Development 129(24):5753-65.

Chuang P.-T.; McMahon A.P. 2003. Branching morphogenesis of the lung: new molecular insights into an old problem. Trends Cell Biol 13(2):86-91.

Chuang P.-T., Kawcak T., McMahon A.P. 2003. Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding Protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes Dev 17(3):342-7.

Chen M.-H., Li Y.-J., Kawakami T., Xu S.-M., Chuang P.-T. 2004. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev 18(6):641-59.

Chen M.-H., Gao N., Kawakami T., Chuang P.-T. 2005. Mice deficient in the Fused homolog do not exhibit phenotypes indicative of perturbed Hedgehog signaling during embryonic development. Mol Cell Biol 25(16):7042-53.

Wilson C.W., Chuang P.-T. 2006. New “hogs” in Hedgehog transport and signal reception. Cell 125(3):435-8.

Mak K.K., Chen M.-H., Day T.F., Chuang P.-T., Yang Y. 2006. Wnt/ß-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development 133(18):3695-707.

Gerber A.N., Wilson C.W., Li Y.-J., Chuang P.-T. 2007. The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation. Oncogene 26(8):1122-36.

Chen M.-H., Wilson C.W., Chuang P.-T. 2007. SnapShot: Hedgehog Signaling Pathway. Cell 130(2):386.

information last updated August 2007

© 2007 The Regents of the University of California. All rights reserved.
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