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 being working on four aspects of the project: (1) The role of Wnt5a as a global cue in establishing chondrocyte polarity in the elongating cartilage. (2) The roles and mechanisms of Wnt/PCP in cartilage and bone development. (3) Wnt signaling regulates liver stem cell self renewal and differentiation. (3) The Wnt/PCP pathway in liver development.

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Project End
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Budget End
Support Year
13
Fiscal Year
2013
Total Cost
$871,113
Indirect Cost
Name
National Human Genome Research Institute
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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
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
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
Malhotra, Deepti; Yang, Yingzi (2014) Wnts' fashion statement: from body stature to dysplasia. Bonekey Rep 3:541
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
Yang, Yingzi (2009) Growth and patterning in the limb: signaling gradients make the decision. Sci Signal 2:pe3
Nemeth, Michael J; Mak, Kingston K; Yang, Yingzi et al. (2009) beta-Catenin expression in the bone marrow microenvironment is required for long-term maintenance of primitive hematopoietic cells. Stem Cells 27:1109-19
Al-Qattan, Mohammad M; Yang, Yingzi; Kozin, Scott H (2009) Embryology of the upper limb. J Hand Surg Am 34:1340-50
Topol, Lilia; Chen, Wen; Song, Hai et al. (2009) Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus. J Biol Chem 284:3323-33

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