Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- beta-katenin genetika metabolismus MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- myši transgenní MeSH
- myši MeSH
- oční proteiny genetika metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- retina cytologie metabolismus MeSH
- retinální pigmentový epitel metabolismus MeSH
- signální dráha Wnt * MeSH
- transdiferenciace buněk MeSH
- transkripční faktor PAX6 MeSH
- transkripční faktory paired box genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- homeodoménové proteiny MeSH
- oční proteiny MeSH
- Pax6 protein, mouse MeSH Prohlížeč
- represorové proteiny MeSH
- transkripční faktor PAX6 MeSH
- transkripční faktory paired box MeSH
Wnt/β-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/β-catenin signaling pathway by analyzing Pax6, β-catenin, and Pax6/β-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 β-catenin. The RPE of a β-catenin/Pax6 double mutant was differentiated into the neural retina; however, the tissue was thinner than that of the conditional β-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.
Zobrazit více v PubMed
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WNT/β-Catenin Signaling in Vertebrate Eye Development
