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Genes Dev 2007 Jul 15;2114:1817-31. doi: 10.1101/gad.1541807.
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TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis.

Ogata S , Morokuma J , Hayata T , Kolle G , Niehrs C , Ueno N , Cho KW .

The molecular mechanisms governing the cell behaviors underlying morphogenesis remain a major focus of research in both developmental biology and cancer biology. TGF-beta ligands control cell fate specification via Smad-mediated signaling. However, their ability to guide cellular morphogenesis in a variety of biological contexts is poorly understood. We report on the discovery of a novel TGF-beta signaling-mediated cellular morphogenesis occurring during vertebrate gastrulation. Activin/nodal members of the TGF-beta superfamily induce the expression of two genes regulating cell adhesion during gastrulation: Fibronectin Leucine-rich Repeat Transmembrane 3 (FLRT3), a type I transmembrane protein containing extracellular leucine-rich repeats, and the small GTPase Rnd1. FLRT3 and Rnd1 interact physically and modulate cell adhesion during embryogenesis by controlling cell surface levels of cadherin through a dynamin-dependent endocytosis pathway. Our model suggests that cell adhesion can be dynamically regulated by sequestering cadherin through internalization, and subsequent redeploying internalized cadherin to the cell surface as needed. As numerous studies have linked aberrant expression of small GTPases, adhesion molecules such as cadherins, and TGF-beta signaling to oncogenesis and metastasis, it is tempting to speculate that this FLRT3/Rnd1/cadherin pathway might also control cell behavior and morphogenesis in adult tissue homeostasis.

PubMed ID: 17639085
PMC ID: PMC1920175
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cer1 flrt1 flrt2 flrt3 fn1 gsc lig1 nodal nodal1 not prss1 rab5a rhoa rnd1 tbxt tgfb1
Antibodies: Flrt3 Ab1
Morpholinos: flrt1 MO1 flrt3 MO1 flrt3 MO2 rnd1 MO1

Article Images: [+] show captions
References [+] :
Adams, Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion. 1996, Pubmed