Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation

Catherine M. Drerup, Heather M. Wiora, Jacek Topczewski, Jill A. Morris*

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

This work reports the characterization and functional analysis of disrupted in schizophrenia 1 (disc1), a well-documented schizophrenia-susceptibility gene, in zebrafish cranial neural crest (CNC). Our data demonstrated that disc1 was expressed in zebrafish CNC cells. Loss of Disc1 resulted in persistent CNC cell medial migration, dorsal to the developing neural epithelium, and hindered migration away from the region dorsal to the neural rod. General CNC cell motility was not affected by Disc1 knockdown, however, as the speed of CNC cells was indistinguishable from that of wild-type counterparts. We determined that the failure of CNC cells to migrate away from the neural rod correlated with the enhanced expression of two transcription factors, foxd3 and sox10. These transcription factors have many functions in CNC cells, including the maintenance of precursor pools, timing of migration onset, and the induction of cell differentiation. Our work, in conjunction with previous studies, suggests that the perpetuation of expression of these factors affects several aspects of CNC cell development, leading to a loss of craniofacial cartilage and an expansion of peripheral cranial glia. Based on our data, we propose a model in which Disc1 functions in the transcriptional repression of foxd3 and sox10, thus mediating CNC cell migration and differentiation.

Original languageEnglish (US)
Pages (from-to)2623-2632
Number of pages10
JournalDevelopment
Volume136
Issue number15
DOIs
StatePublished - Aug 1 2009

Keywords

  • Cranial neural crest
  • Disc1
  • Disrupted in Schizophrenia 1
  • Foxd3
  • Neural crest migration
  • Schizophrenia
  • Sox10
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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