A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination

Development. 2011 Dec;138(23):5177-88. doi: 10.1242/dev.067868. Epub 2011 Oct 26.

Abstract

Epithelial invagination is a common feature of embryogenesis. An example of invagination morphogenesis occurs during development of the early eye when the lens placode forms the lens pit. This morphogenesis is accompanied by a columnar-to-conical cell shape change (apical constriction or AC) and is known to be dependent on the cytoskeletal protein Shroom3. Because Shroom3-induced AC can be Rock1/2 dependent, we hypothesized that during lens invagination, RhoA, Rock and a RhoA guanine nucleotide exchange factor (RhoA-GEF) would also be required. In this study, we show that Rock activity is required for lens pit invagination and that RhoA activity is required for Shroom3-induced AC. We demonstrate that RhoA, when activated and targeted apically, is sufficient to induce AC and that RhoA plays a key role in Shroom3 apical localization. Furthermore, we identify Trio as a RhoA-GEF required for Shroom3-dependent AC in MDCK cells and in the lens pit. Collectively, these data indicate that a Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Shape / physiology*
  • Chick Embryo
  • Cryoultramicrotomy
  • Dogs
  • Electroporation
  • Epithelial Cells / metabolism*
  • Fluorescent Antibody Technique
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Lens, Crystalline / embryology*
  • Mice
  • Microfilament Proteins / metabolism*
  • Morphogenesis / physiology*
  • Phosphoproteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Regression Analysis
  • Signal Transduction / physiology*
  • rho GTP-Binding Proteins / metabolism*
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein

Substances

  • Guanine Nucleotide Exchange Factors
  • Microfilament Proteins
  • Phosphoproteins
  • Shrm protein, mouse
  • Trio protein, mouse
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • RhoA protein, mouse
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein