Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling

Dev Biol. 2012 Jun 15;366(2):232-43. doi: 10.1016/j.ydbio.2012.04.005. Epub 2012 Apr 19.

Abstract

We previously provided evidence that cadherin-6B induces de-epithelialization of the neural crest prior to delamination and is required for the overall epithelial mesenchymal transition (EMT). Furthermore, de-epithelialization induced by cadherin-6B was found to be mediated by BMP receptor signaling independent of BMP. We now find that de-epithelialization is mediated by non-canonical BMP signaling through the BMP type II receptor (BMPRII) and not by canonical Smad dependent signaling through BMP Type I receptor. The LIM kinase/cofilin pathway mediates non-canonical BMPRII induced de-epithelialization, in response to either cadherin-6B or BMP. LIMK1 induces de-epithelialization in the neural tube and dominant negative LIMK1 decreases de-epithelialization induced by either cadherin-6B or BMP. Cofilin is the major known LIMK1 target and a S3A phosphorylation deficient mutated cofilin inhibits de-epithelialization induced by cadherin-6B as well as LIMK1. Importantly, LIMK1 as well as cadherin-6B can trigger ectopic delamination when co-expressed with the competence factor SOX9, showing that this cadherin-6B stimulated signaling pathway can mediate the full EMT in the appropriate context. These findings suggest that the de-epithelialization step of the neural crest EMT by cadherin-6B/BMPRII involves regulation of actin dynamics via LIMK/cofilin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Depolymerizing Factors / physiology
  • Animals
  • Avian Proteins / physiology*
  • Bone Morphogenetic Protein Receptors, Type II / physiology
  • Cadherins / physiology*
  • Chick Embryo
  • Ectoderm / cytology
  • Ectoderm / physiology
  • Epithelial-Mesenchymal Transition / physiology*
  • Lim Kinases / physiology
  • Neural Crest / cytology
  • Neural Crest / physiology*
  • Signal Transduction

Substances

  • Actin Depolymerizing Factors
  • Avian Proteins
  • Cadherins
  • cad6B protein, Gallus gallus
  • Lim Kinases
  • Bone Morphogenetic Protein Receptors, Type II