Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development

0455823 - ÚMG 2016 RIV US eng J - Článek v odborném periodiku
Klímová, Lucie - Antošová, Barbora - Kuželová, Andrea - Strnad, Hynek - Kozmik, Zbyněk
Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development.
Developmental Biology. Roč. 402, č. 1 (2015), s. 48-60. ISSN 0012-1606. E-ISSN 1095-564X
Grant CEP: GA ČR GAP305/11/2198; GA ČR GA15-23675S; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:68378050
Klíčová slova: Pax6 * Onecut * Retina * Horizontal cell
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.155, rok: 2015

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 Onecutl and Onecut2 transcription factors. (C) 2015 Elsevier Inc. All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0256442