Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25794677
DOI
10.1016/j.ydbio.2015.02.023
PII: S0012-1606(15)00116-5
Knihovny.cz E-resources
- Keywords
- Horizontal cell, Onecut, Pax6, Retina,
- MeSH
- Retinal Cone Photoreceptor Cells metabolism MeSH
- Phenotype MeSH
- Hepatocyte Nuclear Factor 6 metabolism MeSH
- Homeodomain Proteins metabolism MeSH
- In Situ Hybridization MeSH
- Stem Cells cytology MeSH
- Molecular Sequence Data MeSH
- Mutation MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Eye Proteins metabolism MeSH
- Repressor Proteins metabolism MeSH
- Retina embryology metabolism MeSH
- Base Sequence MeSH
- Sequence Homology, Nucleic Acid MeSH
- PAX6 Transcription Factor MeSH
- Paired Box Transcription Factors metabolism MeSH
- Transcription Factors metabolism MeSH
- Binding Sites MeSH
- Gene Expression Regulation, Developmental MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hepatocyte Nuclear Factor 6 MeSH
- Homeodomain Proteins MeSH
- Eye Proteins MeSH
- Onecut1 protein, mouse MeSH Browser
- ONECUT2 protein, mouse MeSH Browser
- Pax6 protein, mouse MeSH Browser
- Repressor Proteins MeSH
- PAX6 Transcription Factor MeSH
- Paired Box Transcription Factors MeSH
- Transcription Factors MeSH
Genetic studies of the last decades strongly indicated that generation of particular retinal cell types is governed by gene regulatory networks of transcription factors and their target genes. The paired and homeodomain transcription factor Pax6 plays a pivotal role in retinal development as its inactivation in the retinal progenitor cell population leads to abolished differentiation of all retinal cell types. However, until now, only a few transcription factors operating downstream of Pax6 responsible for generation of individual retinal cell types have been identified. In this study, we identified two transcription factors of the Onecut family, Onecut1 and Onecut2, as Pax6 downstream-acting factors. Onecut1 and Onecut2 were previously shown to be expressed in developing horizontal cells, retinal ganglion cells and cone photoreceptors; however, their role in differentiation of these cell types is poorly understood. In this study, we show that the horizontal cell genesis is severely disturbed in Onecut-deficient retinae. In single Onecut1 and Onecut2 mutants, the number of horizontal cells is dramatically reduced while horizontal cells are completely missing in the Onecut1/Onecut2 compound mutant. Analysis of genes involved in the horizontal cell genesis such as Foxn4, Ptf1a, Prox1 and Lim1 showed that although horizontal cells are initially formed, they are not maintained in Onecut-deficient retinae. Taken together, this study suggests the model in which Pax6 regulates the maintenance of horizontal cells through the activation of Onecut1 and Onecut2 transcription factors.
References provided by Crossref.org
Ancestral role of Pax6 in chordate brain regionalization
Dose-dependent regulation of horizontal cell fate by Onecut family of transcription factors
