Cell-cell signaling is a major strategy that vertebrate embryos employ to control their development. We are interested in the mechanistic understanding of a major signaling pathway mediated by Wnts in the control of vertebrate embryonic development, in particular, limb development and skeletal morphogeneis. Early in limb development, signaling molecules which include the Wnt family members determine where and when the late structures, i.e., skeletal elements will form. Skeletal morphogeneis in the limb occurs through endochondral bone formation in which chondrocytes (they form the cartilage) and osteoblasts (they secrete bone matrix) are differentiated from mesenchymal condensations. This is followed by sequential proliferation and maturation of both chondrocytes and osteoblasts, which are tightly regulated and coordinated to ensure proper morphogenesis of the skeletal system. In the past year, we have found that (1) PTHrP signaling acts downstream of Wnt signlaing in regulating chondrocyte hypetrophy. and that Wnt signlaing regulates the final maturation of hypertrophic chondrocytes independently of PTHrP signaling;(2) Signaling through G proteins play important roles to modulate Wnt signaling activities both in normal development and in diseases;(3) The Wnt/PCP pathway is critical for skeletal morphogenesis. In collaboration with Dr. Bodine, we also found that Wnt/beta catenin signaling in the bone marrow microenviroment is required for long-term maintenance of hematopoietic progenitors.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2009
Total Cost
$1,161,095
Indirect Cost
Name
National Human Genome Research Institute
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Type
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Andre, Philipp; Song, Hai; Kim, Wantae et al. (2015) Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation. Development 142:1516-27
Zhao, Haixia; Zhou, Wenrong; Yao, Zhengju et al. (2015) Foxp1/2/4 regulate endochondral ossification as a suppresser complex. Dev Biol 398:242-54
Qu, Yibo; Huang, Yuhua; Feng, Jia et al. (2014) Genetic evidence that Celsr3 and Celsr2, together with Fzd3, regulate forebrain wiring in a Vangl-independent manner. Proc Natl Acad Sci U S A 111:E2996-3004
Greer, Yoshimi Endo; Westlake, Christopher J; Gao, Bo et al. (2014) Casein kinase 1? functions at the centrosome and Golgi to promote ciliogenesis. Mol Biol Cell 25:1629-40
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Boutin, Camille; Labedan, Paul; Dimidschstein, Jordane et al. (2014) A dual role for planar cell polarity genes in ciliated cells. Proc Natl Acad Sci U S A 111:E3129-38
Malhotra, Deepti; Yang, Yingzi (2014) Wnts' fashion statement: from body stature to dysplasia. Bonekey Rep 3:541
Regard, Jean B; Malhotra, Deepti; Gvozdenovic-Jeremic, Jelena et al. (2013) Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med 19:1505-12
Andre, Philipp; Yang, Yingzi (2013) Reply to Mazzeu: Human mutations in RYK might cause Robinow syndrome. J Biol Chem 288:2906
Gao, Bo; Yang, Yingzi (2013) Planar cell polarity in vertebrate limb morphogenesis. Curr Opin Genet Dev 23:438-44

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