During Xenopus gastrulation, the modulation of adhesive properties within and between the germ layers controls cell-cell and cell-extracellular matrix interactions to regulate morphogenesis. Cell adhesion molecules such as cadherins, protocadherins and integrins have been implicated in the differential regulation of cell adhesion and cell movement. Growth factors known to be involved in mesoderm patterning such as Wnt and activin/nodal also influence mesodermal morphogenesis and cell shape. The focus of this project is to uncover the molecular function of FLRT3 (Fibronectin Leucine-rich Repeat Transmembrane protein 3) in early Xenopus morphogenesis. In the process of uncovering FLRTS's function, we have made the following intriguing observations: First, FLRT3 and Rnd1 are coexpressed in the involuting marginal cells of gastrula stage embryos. Second, overexpression of FLRT3 blocks cadherin-mediated adhesion in the treated cells and this effect requires the presence of Rnd1. Third, FLRT3 interacts physically with Rndl. We now propose to address the following questions to elucidate the molecular mechanisms behind the morphogenetic events mediated by TGF-B signaling:
Aim 1 : How do FLRT3 and Rnd1 function to regulate gastrulation movements? Aim 2: How does FLRT3 interact with Rnd1? Aim 3. How is cadherin-mediated adhesion modulated by FLRT3 and Rnd1? Aim 4: What other molecules mediate FLRT3 and Rndl signaling? This proposal outlines an attempt to delineate the function of the FLRT3 transmembrane protein from the extracellular level down through the intracellular signaling events that affect cell adhesion. Numerous studies have linked aberrant expression of small GTPases and adhesion molecules such as cadherins to oncogenesis and metastasis. As the development of tumors often parallels the process of embryonic development in terms of rapid cell proliferation and extensive cellular movements, our work may provide direct relevance for a better understanding of tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM075018-04S1
Application #
7924292
Study Section
Development - 1 Study Section (DEV)
Program Officer
Haynes, Susan R
Project Start
2009-09-30
Project End
2010-06-30
Budget Start
2009-09-30
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$94,198
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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