Understanding the molecular and cellular events which lead to normal bone formation is an essential prerequisite for understanding the aetiology of skeletal disorders in humans. Further, these insights will enable the design of rational, information-based therapeutic approaches for treating pathological or accidental damage to the skeleton. This proposal sets out to explore the mechanisms underlying key aspects of mammalian skeletogenesis using the mouse as a genetic model.
Aim 1 will examine Ihh's regulatory role in the endochondral skeleton. We will address the significance of Gli3-repression in Ihh signaling and the direct or indirect role of Ihh in regulating PTHrP expression, and thereby chondrocyte maturation. Finally, we will use transcriptional profiling to identify putative targets of Ihh's multiple actions in endochondral skeletal development.
Aim 2 will address the role of Ihh and Wnt signaling in the osteoblast lineage through a step-wise series of genetic manipulations.
Aim 3 will fate map cranial neural crest skeletal precursors as a first step towards examining the relationship between a putative """"""""Fox-code"""""""" and specific skeletal structures of the mammalian face.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK056246-08
Application #
7432429
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2007-06-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
8
Fiscal Year
2007
Total Cost
$408,707
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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