title: Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development.
abstract: 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.
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. Electronic address: lucie.klimova@img.cas.cz.
authors: Lucie
authors: L
authors: Klimova
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. Electronic address: barbora.antosova@img.cas.cz.
authors: Barbora
authors: B
authors: Antosova
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. Electronic address: kuzelova@img.cas.cz.
authors: Andrea
authors: A
authors: Kuzelova
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. Electronic address: hynek.strnad@img.cas.cz.
authors: Hynek
authors: H
authors: Strnad
authors: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14420 Prague 4, Czech Republic. Electronic address: zbynek.kozmik@img.cas.cz.
authors: Zbynek
authors: Z
authors: Kozmik
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051559:Hepatocyte Nuclear Factor 6 / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; C487964:ONECUT2 protein, mouse; C496606:Onecut1 protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: Horizontal cell; Onecut; Pax6; Retina