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Publication : Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.

First Author  van den Berghe V Year  2013
Journal  Neuron Volume  77
Issue  1 Pages  70-82
PubMed ID  23312517 Mgi Jnum  J:197638
Mgi Id  MGI:5494209 Doi  10.1016/j.neuron.2012.11.009
Citation  van den Berghe V, et al. (2013) Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. Neuron 77(1):70-82
abstractText  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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