PUBLICATION
Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina
- Authors
- Clark, A.M., Yun, S., Veien, E.S., Wu, Y.Y., Chow, R.L., Dorsky, R.I., and Levine, E.M.
- ID
- ZDB-PUB-071016-4
- Date
- 2008
- Source
- Brain research 1192(1): 99-113 (Journal)
- Registered Authors
- Clark, Anna, Dorsky, Richard, Veien, Eric
- Keywords
- Homeobox, Homeodomain, Development, Eye, Microphthalmia, Bipolar cell
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Line
- Conserved Sequence/genetics
- Down-Regulation/genetics
- Evolution, Molecular
- Eye Proteins/genetics*
- Gene Expression Regulation, Developmental/genetics*
- Genes, Homeobox/genetics
- Homeodomain Proteins/genetics*
- Humans
- Mice
- Mice, Knockout
- Promoter Regions, Genetic/genetics
- RNA, Messenger/metabolism
- Regulatory Elements, Transcriptional/genetics
- Repressor Proteins/genetics
- Retina/cytology
- Retina/embryology*
- Retina/metabolism*
- Stem Cells/cytology
- Stem Cells/metabolism*
- Transcription Factors/genetics*
- Up-Regulation/genetics
- Vertebrates/embryology
- Zebrafish
- PubMed
- 17919464 Full text @ Brain Res.
Citation
Clark, A.M., Yun, S., Veien, E.S., Wu, Y.Y., Chow, R.L., Dorsky, R.I., and Levine, E.M. (2008) Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain research. 1192(1):99-113.
Abstract
Chx10/Vsx2 and Vsx1 are the only Paired-like CVC (Prd-L:CVC) homeobox genes in the mouse genome. Both are expressed in the retina and have important but distinct roles in retinal development. Mutations in Chx10/Vsx2 cause reduced retinal progenitor cell (RPC) proliferation and an absence of bipolar cells, while mutations in Vsx1 impair differentiation of cone bipolar cells. Given their structural similarities and importance in retinal development, we sought to determine if a regulatory interaction exists between these genes and whether inactivation of both genes blocks initiation of retinal development. We found that Chx10/Vsx2 binds to a specific sequence in the Vsx1 5'-intergenic region and represses the activity of a luciferase reporter under the control of the Vsx1 promoter. This is consistent with our observation that there is an inverse relationship between the levels of Chx10/Vsx2 and Vsx1 immunostaining within the bipolar cell class. Furthermore, Vsx1 mRNA is upregulated in the RPCs of Chx10/Vsx2 deficient mice and zebrafish embryos injected with a chx10/vsx2 morpholino. In mice deficient for both Chx10/Vsx2 and Vsx1 and zebrafish embryos co-injected with chx10/Vsx2 and vsx1 morpholinos, the changes in embryonic retinal development and marker expression are similar in magnitude to embryos with Chx10/Vsx2 loss of function only. From these studies, we propose that Vsx1 is a direct target of Chx10/Vsx2-mediated transcriptional repression. Although Vsx1 mRNA is upregulated in Chx10/Vsx2 deficient RPCs, Vsx1 does not genetically compensate for loss of Chx10/Vsx2, demonstrating that Prd-L:CVC genes, although important, are not absolutely required to initiate retinal development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping