Genetic interaction between Pax6 and β-catenin in the developing retinal pigment epithelium
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- beta Catenin genetics metabolism MeSH
- Homeodomain Proteins genetics metabolism MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Eye Proteins genetics metabolism MeSH
- Repressor Proteins genetics metabolism MeSH
- Retina cytology metabolism MeSH
- Retinal Pigment Epithelium metabolism MeSH
- Wnt Signaling Pathway * MeSH
- Cell Transdifferentiation MeSH
- PAX6 Transcription Factor MeSH
- Paired Box Transcription Factors genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta Catenin MeSH
- Homeodomain Proteins MeSH
- Eye Proteins MeSH
- Pax6 protein, mouse MeSH Browser
- Repressor Proteins MeSH
- PAX6 Transcription Factor MeSH
- Paired Box Transcription Factors 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.
See more in PubMed
Prog Retin Eye Res. 2012 Sep;31(5):351-76 PubMed
PLoS Genet. 2014 May 29;10(5):e1004360 PubMed
Development. 2000 Aug;127(16):3581-91 PubMed
Nat Genet. 1996 Apr;12(4):376-84 PubMed
Development. 2000 Oct;127(20):4325-34 PubMed
Development. 2003 Jul;130(13):2903-15 PubMed
Dev Biol. 2009 Oct 1;334(1):31-45 PubMed
Development. 2014 Mar;141(6):1292-302 PubMed
Neural Dev. 2009 May 05;4:15 PubMed
Exp Eye Res. 2014 Jun;123:141-50 PubMed
Development. 2009 Aug;136(15):2505-10 PubMed
Development. 2001 Jun;128(11):2019-30 PubMed
Development. 2001 Apr;128(8):1253-64 PubMed
Invest Ophthalmol Vis Sci. 2002 May;43(5):1384-8 PubMed
WNT/β-Catenin Signaling in Vertebrate Eye Development
