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, Ruden
AU - Cazzola, Silvia
AU - Berx, Geert
AU - Kessaris, Nicoletta
AU - Vanderhaeghen, Pierre
AU - van Ijcken, Wilfred
AU - Grosveld, Frank
AU - Goossens, Steven
AU - Haigh, Jody
AU - Fishell, Gord James
AU - Goffinet, Andre
AU - Aerts, Stein
AU - Huylebroeck, Danny
AU - Seuntjens, Eve
PY - 2013
Y1 - 2013
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. ? 2013 Elsevier Inc
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. ? 2013 Elsevier Inc
UR - http://www.sciencedirect.com/science/article/pii/S0896627312010008
U2 - 10.1016/j.neuron.2012.11.009
DO - 10.1016/j.neuron.2012.11.009
M3 - Article
SN - 0896-6273
VL - 77
SP - 70
EP - 82
JO - Neuron
JF - Neuron
IS - 1
ER -