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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 as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Journal Nature Genetics
Quellenangaben Volume: 45, Issue: 11, Pages: 1300-1308 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)