Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion. Academic Article uri icon

Overview

abstract

  • Human cleft lip with or without cleft palate (CL/P) is a common craniofacial abnormality caused by impaired fusion of the facial prominences. We have previously reported that, in the mouse embryo, epithelial apoptosis mediates fusion at the seam where the prominences coalesce. Here, we show that apoptosis alone is not sufficient to remove the epithelial layers. We observed morphological changes in the seam epithelia, intermingling of cells of epithelial descent into the mesenchyme and molecular signatures of epithelial-mesenchymal transition (EMT). Utilizing mouse lines with cephalic epithelium-specific Pbx loss exhibiting CL/P, we demonstrate that these cellular behaviors are Pbx dependent, as is the transcriptional regulation of the EMT driver Snail1. Furthermore, in the embryo, the majority of epithelial cells expressing high levels of Snail1 do not undergo apoptosis. Pbx1 loss- and gain-of-function in a tractable epithelial culture system revealed that Pbx1 is both necessary and sufficient for EMT induction. This study establishes that Pbx-dependent EMT programs mediate murine upper lip/primary palate morphogenesis and fusion via regulation of Snail1. Of note, the EMT signatures observed in the embryo are mirrored in the epithelial culture system.

publication date

  • March 1, 2018

Research

keywords

  • Body Patterning
  • Epithelial-Mesenchymal Transition
  • Face
  • Morphogenesis
  • Nose
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Snail Family Transcription Factors

Identity

PubMed Central ID

  • PMC5868993

Scopus Document Identifier

  • 85044259008

Digital Object Identifier (DOI)

  • 10.1038/ncb1173

PubMed ID

  • 29437830

Additional Document Info

volume

  • 145

issue

  • 5