Directed Migration of Cortical Interneurons Depends on the Cell-Autonomous Action of Sip1

Veronique van den Berghe, Elke Stappers, Bram Vandesande, Jordane Dimidschstein, Roel Kroes, Annick Francis, Andrea Conidi, Flore Lesage, Ruben Dries, Silvia Cazzola, Geert Berx, Nicoletta Kessaris, Pierre Vanderhaeghen, Wilfred van IJcken, Frank G. Grosveld, Steven Goossens, Jody J. Haigh, Gord Fishell, André Goffinet, Stein AertsDanny Huylebroeck, Eve Seuntjens

Research output: Contribution to journalArticlepeer-review

Abstract

GABAergic interneurons mainly originate in the medial ganglionic eminence (MGE) of the embryonic ventral telencephalon (VT) and migrate tangentially to the cortex, guided by membrane-bound and secreted factors. We found that Sip1 (Zfhx1b, Zeb2), a transcription factor enriched in migrating cortical interneurons, is required for their proper differentiation and correct guidance. The majority of Sip1 knockout interneurons fail to migrate to the neocortex and stall in the VT. RNA sequencing reveals that Sip1 knockout interneurons do not acquire a fully mature cortical interneuron identity and contain increased levels of the repulsive receptor Unc5b. Focal electroporation of Unc5b-encoding vectors in the MGE of wild-type brain slices disturbs migration to the neocortex, whereas reducing Unc5b levels in Sip1 knockout slices and brains rescues the migration defect. Our results reveal that Sip1, through tuning of Unc5b levels, is essential for cortical interneuron guidance.

Original languageEnglish (US)
Pages (from-to)70-82
Number of pages13
JournalNeuron
Volume77
Issue number1
DOIs
StatePublished - Jan 9 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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