PUBLICATION
Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation
- Authors
- Drerup, C.M., Wiora, H.M., Topczewski, J., and Morris, J.A.
- ID
- ZDB-PUB-090706-20
- Date
- 2009
- Source
- Development (Cambridge, England) 136(15): 2623-2632 (Journal)
- Registered Authors
- Drerup, Katie (Catherine), Topczewski, Jacek
- Keywords
- foxd3, sox10, disc1, Disrupted In Schizophrenia 1, Zebrafish, Cranial neural crest, Neural crest migration, Schizophrenia
- MeSH Terms
-
- Oligonucleotides, Antisense/pharmacology
- Cell Proliferation/drug effects
- Neural Crest/cytology*
- Neural Crest/drug effects
- Skull/cytology
- Skull/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- Cell Differentiation*/drug effects
- Animals
- Neuroglia/cytology
- Neuroglia/metabolism
- Sequence Homology, Amino Acid
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Forkhead Transcription Factors/genetics*
- Forkhead Transcription Factors/metabolism
- SOXE Transcription Factors/genetics*
- SOXE Transcription Factors/metabolism
- Time Factors
- RNA Splice Sites
- Cell Movement*/drug effects
- Zebrafish/embryology*
- Zebrafish/genetics
- Craniofacial Abnormalities/genetics
- Craniofacial Abnormalities/pathology
- Biomarkers/metabolism
- Gene Knockdown Techniques
- Apoptosis/drug effects
- Gene Expression Regulation, Developmental/drug effects
- PubMed
- 19570850 Full text @ Development
Citation
Drerup, C.M., Wiora, H.M., Topczewski, J., and Morris, J.A. (2009) Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development (Cambridge, England). 136(15):2623-2632.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping