Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium

0455800 - ÚMG 2016 RIV DE eng J - Článek v odborném periodiku
Fujimura, Naoko - Klímová, Lucie - Antošová, Barbora - Smolíková, Jana - Machoň, Ondřej - Kozmik, Zbyněk
Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium.
Development Genes and Evolution. Roč. 225, č. 2 (2015), s. 121-128. ISSN 0949-944X. E-ISSN 1432-041X
Grant CEP: GA ČR GAP305/11/2198; GA ČR GAP305/10/2141; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LK11214
Institucionální podpora: RVO:68378050
Klíčová slova: Pax6 * beta-Catenin * Retina * Pigmentation * Transdifferentiation
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 2.508, rok: 2015

Wnt/beta-catenin signaling plays an essential role in the retinal pigment epithelium (RPE) determination. Since activity of Pax6 (together with Pax2) is also required for the RPE determination, we investigated a possible genetic interaction between Pax6 and Wnt/beta-catenin signaling pathway by analyzing Pax6, beta-catenin, and Pax6/beta-catenin conditional knockout mice. Although Pax6 inactivation alone had no impact on initial specification determined by the expression of Mitf and Otx2, melanin pigmentation was reduced in the RPE. This suggests that along with Mitf and Otx2, Pax6 is required for the full differentiation of RPE. Reporter gene assays in vitro suggest that hypopigmentation is at least in part due to the direct regulation of genes encoding enzymes involved in melanin synthesis by Pax6, Mitf, and beta-catenin. The RPE of a beta-catenin/Pax6 double mutant was differentiated into the neural retina; however, the tissue was thinner than that of the conditional beta-catenin mutant due to reduced proliferation. Together, our data demonstrate that Pax6 is required for the RPE differentiation by regulating pigmentation and accountable for hyperproliferation in the transdifferentiated RPE. In this context, Pax6 appears to function as a pleiotropic regulator, directing development of ocular tissues in concert with the signaling pathway and, at the same time, regulating expression of structural component of the eye, such as shielding pigment.
Trvalý link: http://hdl.handle.net/11104/0256417