[en] The neocortex is stereotypically organized into layers of excitatory neurons arranged in a precise parallel orientation. Here we show that dynamic adhesion both preceding and following radial migration is essential for this organization. Neuronal adhesion is regulated by the Mowat-Wilson syndrome-associated transcription factor Zeb2 (Sip1/Zfhx1b) through direct repression of independent adhesion pathways controlled by Neuropilin-1 (Nrp1) and Cadherin-6 (Cdh6). We reveal that to initiate radial migration, neurons must first suppress adhesion to the extracellular matrix. Zeb2 regulates the multipolar stage by transcriptional repression of Nrp1 and thereby downstream inhibition of integrin signaling. Upon completion of migration, neurons undergo an orientation process that is independent of migration. The parallel organization of neurons within the neocortex is controlled by Cdh6 through atypical regulation of integrin signaling via its RGD motif. Our data shed light on the mechanisms that regulate initiation of radial migration and the postmigratory orientation of neurons during neocortical development.
Epifanova, Ekaterina ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
Salina, Valentina ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, ; Institute of Neuroscience, Lobachevsky University of Nizhny Novgorod, Nizhny
Lajkó, Denis; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Textoris-Taube, Kathrin; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Naumann, Thomas; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Bormuth, Olga; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Bormuth, Ingo; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Horan, Stephen; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Schaub, Theres ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
Borisova, Ekaterina ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, ; Institute of Neuroscience, Lobachevsky University of Nizhny Novgorod, Nizhny
Ambrozkiewicz, Mateusz C ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
Tarabykin, Victor ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, ; Institute of Neuroscience, Lobachevsky University of Nizhny Novgorod, Nizhny
Rosário, Marta ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
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