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Pfurr, S.* ; Chu, Y.H.* ; Bohrer, C.* ; Greulich, F. ; Beattie, R.* ; Mammadzada, K.* ; Hils, M.* ; Arnold, S.J.* ; Taylor, V.* ; Schachtrup, K.* ; Uhlenhaut, N.H. ; Schachtrup, C.*

The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development.

Development 144, 3917-3931 (2017)
Verlagsversion Postprint DOI PMC
Open Access Green
During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.5, while depletion of the alternatively spliced E12 variant did not affect layer-specific neurogenesis. While ChIP-Seq identified a big overlap for E12- and E47-specific binding sites in embryonic NSCs, including sites at the cyclin-dependent kinase inhibitor (CDKI) Cdkn1c gene locus, RNA-Seq revealed a unique transcriptional regulation by each splice variant. E47 activated the expression of the CDKI Cdkn1c through binding to a distal enhancer. Finally, overexpression of E47 in embryonic NSCs in vitro impaired neurite outgrowth and E47 overexpression in vivo by in utero electroporation disturbed proper layer-specific neurogenesis and upregulated p57(KIP2) expression. Overall, this study identified E2A target genes in embryonic NSCs and demonstrates that E47 regulates neuronal differentiation via p57(KIP2).
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Basic Helix-loop-helix Transcription Factor ; Cell Cycle Regulation ; Cortical Neurogenesis ; E2a ; Enhancer ; Neurite Outgrowth ; P57(kip2); Neural Stem-cells; Beckwith-wiedemann-syndrome; Loop-helix Proteins; Developing Cerebral-cortex; Developing Neocortex; Dna-binding; Ventral Telencephalon; Transcription Factors; Brain-development; Laminar Identity
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Zeitschrift Development / Company of Biologists
Quellenangaben Band: 144, Heft: 21, Seiten: 3917-3931 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Verlagsort Cambridge
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)