title: 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.
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.
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, PO Box 800732, Charlottesville, VA 22908, USA. kisookpark@khu.ac.kr
authors.forename: Ki-Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Barry M
authors.initials: BM
authors.lastname: Gumbiner
mesh_terms: D051339:Actin Depolymerizing Factors / Q000502:physiology; D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000502:physiology; D015820:Cadherins / Q000502:physiology*; D002642:Chick Embryo; D004475:Ectoderm / Q000166:cytology / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D054461:Lim Kinases / Q000502:physiology; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D051339:Actin Depolymerizing Factors; D030161:Avian Proteins; D015820:Cadherins; C094293:cad6B protein, Gallus gallus; D054461:Lim Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II