@article{e6e7610a2e364714bd80707ab0fe406f,
title = "Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development",
abstract = "The regulated proliferation and differentiation of neural stem cells before the generation and migration of neurons in the cerebral cortex are central aspects of mammalian development. Periventricular neuronal heterotopia, a specific form of mislocalization of cortical neurons, can arise from neuronal progenitors that fail to negotiate aspects of these developmental processes. Here we show that mutations in genes encoding the receptor-ligand cadherin pair DCHS1 and FAT4 lead to a recessive syndrome in humans that includes periventricular neuronal heterotopia. Reducing the expression of Dchs1 or Fat4 within mouse embryonic neuroepithelium increased progenitor cell numbers and reduced their differentiation into neurons, resulting in the heterotopic accumulation of cells below the neuronal layers in the neocortex, reminiscent of the human phenotype. These effects were countered by concurrent knockdown of Yap, a transcriptional effector of the Hippo signaling pathway. These findings implicate Dchs1 and Fat4 upstream of Yap as key regulators of mammalian neurogenesis.",
author = "Silvia Cappello and Gray, {Mary J.} and Caroline Badouel and Simona Lange and Melanie Einsiedler and Myriam Srour and David Chitayat and Hamdan, {Fadi F.} and Jenkins, {Zandra A.} and Tim Morgan and Nadia Preitner and Tami Uster and Jackie Thomas and Patrick Shannon and Victoria Morrison and {Di Donato}, Nataliya and {Van Maldergem}, Lionel and Teresa Neuhann and Ruth Newbury-Ecob and Marielle Swinkells and Paulien Terhal and Wilson, {Louise C.} and Zwijnenburg, {Petra J.G.} and Sutherland-Smith, {Andrew J.} and Black, {Michael A.} and David Markie and Michaud, {Jacques L.} and Simpson, {Michael A.} and Sahar Mansour and Helen McNeill and Magdalena G{\"o}tz and Robertson, {Stephen P.}",
note = "Funding Information: We thank the families participating in this study for their involvement. This work was supported by funding from Cure Kids New Zealand and the Health Research Council of New Zealand (10/402) (S.P.R.), the Department of Health through the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy{\textquoteright}s and St. Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London and King{\textquoteright}s College Hospital NHS Foundation Trust (M.A.S.), Deutsche Forschungsgemeinschaft:SFB 817, Synergy and the Bundesministerium f{\"u}r Bildung und Forschung (M.G. and S.C.). The human embryonic and fetal material was provided by the joint Medical Research Council (grant G0700089)/Wellcome Trust (grant GR082557) Human Developmental Biology Resource. We thank F. Calzolari for the design of the Yap miRNA, P. Malatesta (Department of Experimental Medicine (DiMES), University of Genoa), K. Guan (Life Sciences Institute, University of Michigan) and S. Piccolo (Department of Molecular Medicine, University of Padua School of Medicine) for sharing plasmids and T. {\"O}zt{\"u}rk and A. Waiser for excellent technical support.",
year = "2013",
month = nov,
doi = "10.1038/ng.2765",
language = "English",
volume = "45",
pages = "1300--1310",
journal = "Nature Genetics",
issn = "1061-4036",
number = "11",
}