Article abstract
Nature Cell Biology 10, 765 - 775 (2008)
Published online: 15 June 2008 | doi:10.1038/ncb1739
There is an Erratum (August 2008) associated with this Article.
RhoA and microtubule dynamics control cell–basement membrane interaction in EMT during gastrulation
Yukiko Nakaya1, Erike W. Sukowati1, Yuping Wu1 & Guojun Sheng1
Abstract
Molecular and cellular mechanisms of epithelial–mesenchymal transition (EMT), crucial in development and pathogenesis, are still poorly understood. Here we provide evidence that distinct cellular steps of EMT occur sequentially during gastrulation. Basement membrane (BM) breakdown is the first recognizable step and is controlled by loss of basally localized RhoA activity and its activator neuroepithelial-transforming-protein-1 (Net1). Failure of RhoA downregulation during EMT leads to BM retention and reduction of its activity in normal epithelium leads to BM breakdown. We also show that this is in part mediated by RhoA-regulated basal microtubule stability. Microtubule disruption causes BM breakdown and its stabilization results in BM retention. We propose that loss of Net1 before EMT reduces basal RhoA activity and destabilizes basal microtubules, causing disruption of epithelial cell–BM interaction and subsequently, breakdown of the BM.
- Laboratory for Early Embryogenesis, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
Correspondence to: Guojun Sheng1 e-mail: sheng@cdb.riken.jp
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