title: TBX1 regulates epithelial polarity and dynamic basal filopodia in the second heart field.
abstract: Elongation of the vertebrate heart occurs by progressive addition of second heart field (SHF) cardiac progenitor cells from pharyngeal mesoderm to the poles of the heart tube. The importance of these cells in the etiology of congenital heart defects has led to extensive research into the regulation of SHF deployment by signaling pathways and transcription factors. However, the basic cellular features of these progenitor cells, including epithelial polarity, cell shape and cell dynamics, remain poorly characterized. Here, using immunofluorescence, live imaging and embryo culture, we demonstrate that SHF cells constitute an atypical, apicobasally polarized epithelium in the dorsal pericardial wall, characterized by apical monocilia and dynamic actin-rich basal filopodia. We identify the 22q11.2 deletion syndrome gene Tbx1, required in the SHF for outflow tract development, as a regulator of the epithelial properties of SHF cells. Cell shape changes in mutant embryos include increased circularity, a reduced basolateral membrane domain and impaired filopodial activity, and are associated with elevated aPKCζ levels. Activation of aPKCζ in embryo culture similarly impairs filopodia activity and phenocopies proliferative defects and ectopic differentiation observed in the SHF of Tbx1 null embryos. Our results reveal that epithelial and progenitor cell status are coupled in the SHF, identifying control of cell shape as a regulatory step in heart tube elongation and outflow tract morphogenesis.
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille 13288, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Francou
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille 13288, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Saint-Michel
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille 13288, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Mesbah
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille 13288, France Robert.Kelly@univ-amu.fr.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Kelly
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016764:Cell Polarity / Q000502:physiology*; D004062:DiGeorge Syndrome / Q000235:genetics; D004848:Epithelium / Q000196:embryology*; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; C115015:PKC-3 protein; D011493:Protein Kinase C
keywords: Apicobasal polarity; Cardiac progenitor cells; Mouse; TBX1