title: Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development.
abstract: 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 "Conditional by Inversion" Sox2 allele (Sox2(COIN) ) has been employed to generate an epiblast ablation of Sox2 function (Sox2(EpINV) ). Sox2 (EpINV/+(H)) haploinsufficient and conditional (Sox2(EpINV/mosaic) ) 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(+) NCC in the branchial arches and frontonasal process of the Sox2 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.
authors.affiliation: Stem Cell Biology Laboratory, Division of Molecular Biology and Genetics, Biomedical Sciences Research Centre "Alexander Fleming" Vari-Attica, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mandalos
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U964, CNRS, UMR7104, Université de Strasbourg Illkirch, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rhinn
authors.affiliation: Orofacial Development and Regeneration Unit, Faculty of Medicine, Institute of Oral Biology, University of Zurich, ZZM Zurich, Switzerland.
authors.forename: Zoraide
authors.initials: Z
authors.lastname: Granchi
authors.affiliation: Stem Cell Biology Laboratory, Division of Molecular Biology and Genetics, Biomedical Sciences Research Centre "Alexander Fleming" Vari-Attica, Greece ; Department of Neurosurgery, University Hospitals Case Medical Center Cleveland, OH, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karampelas
authors.affiliation: Orofacial Development and Regeneration Unit, Faculty of Medicine, Institute of Oral Biology, University of Zurich, ZZM Zurich, Switzerland.
authors.forename: Thimios
authors.initials: T
authors.lastname: Mitsiadis
authors.affiliation: Regeneron Pharmaceuticals Tarrytown, New York, NY, USA.
authors.forename: Aris N
authors.initials: AN
authors.lastname: Economides
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U964, CNRS, UMR7104, Université de Strasbourg Illkirch, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.affiliation: Stem Cell Biology Laboratory, Division of Molecular Biology and Genetics, Biomedical Sciences Research Centre "Alexander Fleming" Vari-Attica, Greece.
authors.forename: Eumorphia
authors.initials: E
authors.lastname: Remboutsika
keywords: Sox genes; SoxB; craniofacial development; heterochrony; neural progenitors; neurocristopathies; stem cells