title: RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic eminence ventricular zone for proper cortical interneuron migration.
abstract: Cortical interneurons arise from the ganglionic eminences in the ventral telencephalon and migrate tangentially to the cortex. Although RhoA and Cdc42, members of the Rho family of small GTPases, have been implicated in regulating neuronal migration, their respective roles in the tangential migration of cortical interneurons remain unknown. Here we show that loss of RhoA and Cdc42 in the ventricular zone (VZ) of the medial ganglionic eminence (MGE) using Olig2-Cre mice causes moderate or severe defects in the migration of cortical interneurons, respectively. Furthermore, RhoA- or Cdc42-deleted MGE cells exhibit impaired migration in vitro. To determine whether RhoA and Cdc42 directly regulate the motility of cortical interneurons during migration, we deleted RhoA and Cdc42 in the subventricular zone (SVZ), where more fate-restricted progenitors are located within the ganglionic eminences, using Dlx5/6-Cre-ires-EGFP (Dlx5/6-CIE) mice. Deletion of either gene within the SVZ does not cause any obvious defects in cortical interneuron migration, indicating that cell motility is not dependent upon RhoA or Cdc42. These findings provide genetic evidence that RhoA and Cdc42 are required in progenitors of the MGE in the VZ, but not the SVZ, for proper cortical interneuron migration.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. katayama-vet@umin.ac.jp
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Katayama
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Imai
authors.forename: Kenneth
authors.initials: K
authors.lastname: Campbell
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D007395:Interneurons / Q000378:metabolism*; D008473:Median Eminence / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009415:Nerve Net / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis; D000076104:Oligodendrocyte Transcription Factor 2; D011247:Pregnancy; D020764:cdc42 GTP-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C581598:Cdc42 protein, mouse; C512773:Olig2 protein, mouse; C526380:RhoA protein, mouse
keywords: Cdc42; Interneuron; Mouse; RhoA; Tangential migration