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First published online 1 July 2009
doi: 10.1242/dev.030577

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

¹ Program in Human Molecular Genetics, Department of Pediatrics, Feinberg School of Medicine, Children's Memorial Research Center, Northwestern University, 2300 Children's Plaza, Box 211, Chicago, IL 60614, USA.
² Program in Developmental Biology, Department of Pediatrics, Feinberg School of Medicine, Children's Memorial Research Center, Northwestern University, 2300 Children's Plaza, Box 211, Chicago, IL 60614, USA.

^* Author for correspondence (e-mail: j-morris4{at}northwestern.edu)

Accepted 3 June 2009

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.

Key words: foxd3, sox10, disc1, Disrupted In Schizophrenia 1, Zebrafish, Cranial neural crest, Neural crest migration, Schizophrenia

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				N. J. Brandon, J. K. Millar, C. Korth, H. Sive, K. K. Singh, and A. Sawa Understanding the Role of DISC1 in Psychiatric Disease and during Normal Development J. Neurosci., October 14, 2009; 29(41): 12768 - 12775. [Abstract] [Full Text] [PDF]