Adhesion dynamics in the neocortex determine the start of migration and the post-migratory orientation of neurons

Ekaterina Epifanova; Valentina Salina; Denis Lajkó; Kathrin Textoris-Taube; Thomas Naumann; Olga Bormuth; Ingo Bormuth; Stephen Horan; Theres Schaub; Ekaterina Borisova; Mateusz C Ambrozkiewicz; Victor Tarabykin; Marta Rosário

doi:10.1126/sciadv.abf1973

Adhesion dynamics in the neocortex determine the start of migration and the post-migratory orientation of neurons

Sci Adv. 2021 Jul 2;7(27):eabf1973. doi: 10.1126/sciadv.abf1973. Print 2021 Jul.

Authors

Affiliations

¹ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Cell and Neurobiology, Charitéplatz 1, 10117 Berlin, Germany.
² Institute of Neuroscience, Lobachevsky University of Nizhny Novgorod, Nizhny Novgorod 603950, Russian Federation.
³ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Biochemistry, Core Facility High-Throughput Mass Spectrometry, Charitéplatz 1, 10117 Berlin, Germany.
⁴ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Functional Neuroanatomy, Charitéplatz 1, 10117 Berlin, Germany.
⁵ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Cell and Neurobiology, Charitéplatz 1, 10117 Berlin, Germany. marta.rosario@charite.de.

PMID: 34215578
DOI: 10.1126/sciadv.abf1973

Abstract

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.

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