TY - JOUR
T1 - Directed Migration of Cortical Interneurons Depends on the Cell-Autonomous Action of Sip1
AU - van den Berghe, Veronique
AU - Stappers, Elke
AU - Vandesande, Bram
AU - Dimidschstein, Jordane
AU - Kroes, Roel
AU - Francis, Annick
AU - Conidi, Andrea
AU - Lesage, Flore
AU - Dries, Ruben
AU - Cazzola, Silvia
AU - Berx, Geert
AU - Kessaris, Nicoletta
AU - Vanderhaeghen, Pierre
AU - van IJcken, Wilfred
AU - Grosveld, Frank G.
AU - Goossens, Steven
AU - Haigh, Jody J.
AU - Fishell, Gord
AU - Goffinet, André
AU - Aerts, Stein
AU - Huylebroeck, Danny
AU - Seuntjens, Eve
N1 - Funding Information:
We thank K. Campbell and R. Klein for sharing mouse lines. We also thank D.J. Anderson, C. Birchmeier, K. Campbell, B. Condie, J. Egea, A. Eichmann, Z. Kaprielian, R. Klein, and M. Price for sharing plasmids and reagents, V. Van Duppen for FACS-sorting, and A. van der Sloot for RNA sequencing. We appreciate the advice of A. Gaertner and all members of the A. Zwijsen and DH labs, and H. Kondoh and Y. Higashi for previous important contributions. This work was funded by the Research Council of KU Leuven (OT-09/053 and GOA-11/012, to D.H.), FWO-V (G.0954.11N, to D.H. and E. Seuntjens), the Queen Elisabeth Medical Foundation (to P.V.; and GSKE 1113, to D.H. and E. Seuntjens), the Interuniversity Attraction Poles (IUAP-VI/20 funding to D.H., A.G., and P.V., and IUAP-VII/07 funding to D.H.), the InfraMouse Grant from the Hercules Foundation (ZW09-03, to D.H.), the visiting professor program from the Royal Netherlands Academy of Arts and Sciences (to D.H.), and the intercommunity visiting program of the Francqui Foundation (to E. Seuntjens and A.G.). The N.K. lab is funded by the European Research Council (ERC-STG 207807) and the Wellcome Trust. Work from P.V. was supported by the Action de Recherches Concertées (ARC) Programs of the Communauté Wallonie/Bruxelles, the Federal Office for Scientific, Technical and Cultural Affairs, the FNRS, and Welbio and Programme d’Excellence CIBLES of the Walloon Region. P.V. is a FNRS Research Director, J.D. was a FRIA Research Fellow, and S.G. is supported by FWO. V.vdB., E. Stappers, and R.D. are supported by the Agency for Innovation by Science and Technology (IWT).
PY - 2013/1/9
Y1 - 2013/1/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2012.11.009
DO - 10.1016/j.neuron.2012.11.009
M3 - Article
C2 - 23312517
AN - SCOPUS:84872193597
SN - 0896-6273
VL - 77
SP - 70
EP - 82
JO - Neuron
JF - Neuron
IS - 1
ER -