The objective of the Program is to study the molecular regulation of the outgrowth, patterning, and regeneration of the developing vertebrate limb. In Project 1, the hypothesis that the extracellular macromolecule hyaluronan (HA) facilitates the outgrowth, proliferation, and directed migration of limb mesenchymal cells in response to the apical ectodermal ridge (AER) will be investigated, as will the hypothesis that HA acts in concert with the EGFR/ErbB signaling network in the regulation of limb outgrowth and patterning. The role of HA in regulating the onset of limb cartilage differentiation will also be studied, as will its role in AER activity. In Project 2, the roles of the EGFR/ErbB family of tyrosine kinase receptors and ligands in the formation and function of the AER and in the signaling pathways that control limb patterning along the anteroposterior and dorsoventral axes will be investigated, as will role of EGFR/ErbB signaling in the programmed cell death involved in shaping limb contours. In Project 3, the cellular and molecular mechanisms that regulate digit tip regeneration in the embryonic mouse limb bud and the AER-dependent regeneration of the chick limb bud will be studied. In particular, the roles of directed cell migration and differential cell adhesion in the regeneration response will be investigated, as will the roles and relationships among Dlx genes, Msx genes, BMP signaling, FGFs, EGFR/ErbB signaling, and hyaluronan in the control of mammalian digit tip and chick limb bud regeneration. The Projects will be supported by an Administrative Core (Core A) that will manage the financial aspects of the research budgets.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD022610-19
Application #
7616126
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (KR))
Program Officer
Javois, Lorette Claire
Project Start
1997-02-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
19
Fiscal Year
2009
Total Cost
$777,502
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Lee, Jangwoo; Corcoran, Amy; Han, Manjong et al. (2013) Dlx5 and Msx2 regulate mouse anterior neural tube closure through ephrinA5-EphA7. Dev Growth Differ 55:341-9
Shepard, John B; Jeong, Jae-Wook; Maihle, Nita J et al. (2013) Transient anabolic effects accompany epidermal growth factor receptor signal activation in articular cartilage in vivo. Arthritis Res Ther 15:R60
Yu, Ling; Han, Manjong; Yan, Mingquan et al. (2012) BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center. Dev Biol 372:263-73
Özpolat, B Duygu; Zapata, Mariana; Daniel Frugé, John et al. (2012) Regeneration of the elbow joint in the developing chick embryo recapitulates development. Dev Biol 372:229-38
Wang, Chi-Kuang Leo; Tsugane, Mizuyo H; Scranton, Victoria et al. (2011) Pleiotropic patterning response to activation of Shh signaling in the limb apical ectodermal ridge. Dev Dyn 240:1289-302
Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline et al. (2009) Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development 136:2825-35
Stefanov, Emily K; Ferrage, Jordan M; Parchim, Nicholas F et al. (2009) Modification of the zone of polarizing activity signal by trypsin. Dev Growth Differ 51:123-33
Li, Haitao; Marijanovic, Inga; Kronenberg, Mark S et al. (2008) Expression and function of Dlx genes in the osteoblast lineage. Dev Biol 316:458-70
Muneoka, Ken; Allan, Christopher H; Yang, Xiaodong et al. (2008) Mammalian regeneration and regenerative medicine. Birth Defects Res C Embryo Today 84:265-80
Han, Manjong; Yang, Xiaodong; Lee, Jangwoo et al. (2008) Development and regeneration of the neonatal digit tip in mice. Dev Biol 315:125-35

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