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Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium
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SYSNO ASEP 0455800 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium Tvůrce(i) Fujimura, Naoko (UMG-J)
Klímová, Lucie (UMG-J)
Antošová, Barbora (UMG-J)
Smolíková, Jana (UMG-J) RID
Machoň, Ondřej (UMG-J) RID
Kozmik, Zbyněk (UMG-J) RIDZdroj.dok. Development Genes and Evolution - ISSN 0949-944X
Roč. 225, č. 2 (2015), s. 121-128Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova Pax6 ; beta-Catenin ; Retina ; Pigmentation ; Transdifferentiation Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP305/11/2198 GA ČR - Grantová agentura ČR GAP305/10/2141 GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LK11214 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMG-J - RVO:68378050 UT WOS 000351605300006 DOI 10.1007/s00427-015-0493-4 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2016
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