title: Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice.
abstract: BACKGROUND
  Tangential migration presents the primary mode of migration of cortical interneurons translocating into the cerebral cortex from subpallial domains. This migration takes place in multiple streams with the most superficial one located in the cortical marginal zone. While a number of forebrain-expressed molecules regulating this process have emerged, it remains unclear to what extent structures outside the brain, like the forebrain meninges, are involved.
  
  
  RESULTS
  We studied a unique Foxc1 hypomorph mouse model (Foxc1hith/hith) with meningeal defects and impaired tangential migration of cortical interneurons. We identified a territorial correlation between meningeal defects and disruption of interneuron migration along the adjacent marginal zone in these animals, suggesting that impaired meningeal integrity might be the primary cause for the observed migration defects. Moreover, we postulate that the meningeal factor regulating tangential migration that is affected in homozygote mutants is the chemokine Cxcl12. In addition, by using chromatin immunoprecipitation analysis, we provide evidence that the Cxcl12 gene is a direct transcriptional target of Foxc1 in the meninges. Further, we observe migration defects of a lesser degree in Cajal-Retzius cells migrating within the cortical marginal zone, indicating a less important role for Cxcl12 in their migration. Finally, the developmental migration defects observed in Foxc1hith/hith mutants do not lead to obvious differences in interneuron distribution in the adult if compared to control animals.
  
  
  CONCLUSIONS
  Our results suggest a critical role for the forebrain meninges to promote during development the tangential migration of cortical interneurons along the cortical marginal zone and Cxcl12 as the factor responsible for this property.
authors.affiliation: Institute of Pediatric Regenerative Medicine Shriners Hospitals for Children, Northern California, 2425 Stockton Blvd., CA 95817, USA. kzarbalis@ucdavis.edu
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarbalis
authors.forename: Youngshik
authors.initials: Y
authors.lastname: Choe
authors.forename: Julie A
authors.initials: JA
authors.lastname: Siegenthaler
authors.forename: Lori A
authors.initials: LA
authors.lastname: Orosco
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000166:cytology; D054377:Chemokine CXCL12 / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics*; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D008297:Male; D008588:Meningocele / Q000150:complications / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology*; D061251:Primary Cell Culture
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse