AUTHOR=Mandalos Nikolaos , Rhinn Muriel , Granchi Zoraide , Karampelas Ioannis , Mitsiadis Thimios , Economides Aris N. , Dollé Pascal , Remboutsika Eumorphia 

TITLE=Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development

JOURNAL=Frontiers in Physiology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00345

DOI=10.3389/fphys.2014.00345

ISSN=1664-042X

ABSTRACT=<p>Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC) pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A “<italic>Co</italic>nditional by <italic>In</italic>version” <italic>Sox2</italic> allele (<italic>Sox2<sup>COIN</sup></italic>) has been employed to generate an epiblast ablation of Sox2 function (<italic>Sox2<sup>EpINV</sup></italic>). <italic>Sox2</italic><sup><italic>EpINV</italic>/+<italic>(H)</italic></sup> haploinsufficient and conditional (<italic>Sox2<sup>EpINV/mosaic</sup></italic>) mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10<sup>+</sup> NCC in the branchial arches and frontonasal process of the <italic>Sox2</italic> mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions (EMT) that are important for the cell flow in the developing head.</p>