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Cappello, S. ; Gray, M.J.* ; Badouel, C.* ; Lange, S. ; Einsiedler, M. ; Srour, M.* ; Chitayat, D.* ; Hamdan, F.F.* ; Jenkins, Z.A.* ; Morgan, T.* ; Preitner, N.* ; Uster, T.* ; Thomas, J.* ; Shannon, P.* ; Morrison, V.* ; di Donato, N.* ; van Maldergem, L.* ; Neuhann, T.* ; Newbury-Ecob, R.* ; Swinkells, M.* ; Terhal, P.* ; Wilson, L.C.* ; Zwijnenburg, P.J.* ; Sutherland-Smith, A.J.* ; Black, M.A.* ; Markie, D.* ; Michaud, J.L.* ; Simpson, M.A.* ; Mansour, S.* ; McNeill, H.* ; Götz, M. ; Robertson, S.P.*

Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development.

Nat. Genet. 45, 1300-1308 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Van Maldergem Syndrome ; Planar Cell Polarity ; Neuronal Migration ; Signaling Pathway ; Hippo Pathway ; Beta-catenin ; Radial Glia ; Filamin-a ; Periventricular Heterotopia ; Developing Neocortex
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 45, Heft: 11, Seiten: 1300-1308 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)