title: Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
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.
authors: Laboratory of Molecular Biology (Celgen), Department of Development and Regeneration, University of Leuven, 3000 Leuven, Belgium.
authors: Veronique
authors: V
authors: van den Berghe
authors: Elke
authors: E
authors: Stappers
authors: Bram
authors: B
authors: Vandesande
authors: Jordane
authors: J
authors: Dimidschstein
authors: Roel
authors: R
authors: Kroes
authors: Annick
authors: A
authors: Francis
authors: Andrea
authors: A
authors: Conidi
authors: Flore
authors: F
authors: Lesage
authors: Ruben
authors: R
authors: Dries
authors: Silvia
authors: S
authors: Cazzola
authors: Geert
authors: G
authors: Berx
authors: Nicoletta
authors: N
authors: Kessaris
authors: Pierre
authors: P
authors: Vanderhaeghen
authors: Wilfred
authors: W
authors: van Ijcken
authors: Frank G
authors: FG
authors: Grosveld
authors: Steven
authors: S
authors: Goossens
authors: Jody J
authors: JJ
authors: Haigh
authors: Gord
authors: G
authors: Fishell
authors: André
authors: A
authors: Goffinet
authors: Stein
authors: S
authors: Aerts
authors: Danny
authors: D
authors: Huylebroeck
authors: Eve
authors: E
authors: Seuntjens
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development*; D055786:Gene Knockout Techniques; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D000075386:Netrin Receptors; D009924:Organ Culture Techniques; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development
chemical_list: D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; C491561:Sip1 protein, mouse