Open AccessFace morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion
Author(s) -
Marta Losa,
Maurizio Risolino,
Bingsi Li,
James Hart,
Laura Quintana,
Irina Grishina,
Hui Yang,
Irene Choi,
Patrick Lewicki,
Sameer ud Dowla Khan,
Robert Aho,
Jennifer M. Feenstra,
C. Theresa Vincent,
Anthony M. Brown,
Elisabetta Ferretti,
Trevor Williams,
Licia Selleri
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.157628
Subject(s) - biology , morphogenesis , anatomy , microbiology and biotechnology , face (sociological concept) , evolutionary biology , genetics , gene , social science , sociology
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.