PUBLICATION
Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish
- Authors
- Antonellis, A., Huynh, J.L., Lee-Lin, S.Q., Vinton, R.M., Renaud, G., Loftus, S.K., Elliot, G., Wolfsberg, T.G., Green, E.D., McCallion, A.S., and Pavan, W.J.
- ID
- ZDB-PUB-080908-16
- Date
- 2008
- Source
- PLoS Genetics 4(9): e1000174 (Journal)
- Registered Authors
- McCallion, Andy
- Keywords
- Zebrafish, Mammalian genomics, Gene expression, Sequence motif analysis, Reporter genes, Embryos, Melanocytes, Mouse models
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Binding Sites
- Conserved Sequence
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/metabolism
- Embryo, Nonmammalian/metabolism
- Enhancer Elements, Genetic*
- Gene Transfer Techniques
- Genome
- High Mobility Group Proteins/genetics*
- High Mobility Group Proteins/metabolism
- Melanocytes/metabolism
- Mice
- Mice, Transgenic
- NIH 3T3 Cells
- Neural Crest/metabolism*
- Neuroglia/cytology
- Neuroglia/metabolism*
- SOXE Transcription Factors
- Schwann Cells/metabolism
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 18773071 Full text @ PLoS Genet.
Citation
Antonellis, A., Huynh, J.L., Lee-Lin, S.Q., Vinton, R.M., Renaud, G., Loftus, S.K., Elliot, G., Wolfsberg, T.G., Green, E.D., McCallion, A.S., and Pavan, W.J. (2008) Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish. PLoS Genetics. 4(9):e1000174.
Abstract
Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest-derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping