PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF

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It is currently poorly understood how a single developmental transcription regulator controls early specification as well as a broad range of highly specialized differentiation schemes. PAX6 is one of the most extensively investigated factors in central nervous system development, yet its role in execution of lineage-specific programs remains mostly elusive. Here, we directly investigated the involvement of PAX6 in the differentiation of one lineage, the retinal pigmented epithelium (RPE), a neuroectodermal-derived tissue that is essential for retinal development and function. We revealed that PAX6 accomplishes its role through a unique regulatory interaction with the transcription factor MITF, a master regulator of the pigmentation program. During the differentiation of the RPE, PAX6 regulates the expression of an RPE-specific isoform of Mitf and importantly, at the same time, PAX6 functions together with MITF to directly activate the expression of downstream genes required for pigment biogenesis. These findings provide comprehensive insight into the gene hierarchy that controls RPE development: from a kernel gene (a term referring to the upper-most gene in the gene regulatory network) that is broadly expressed during CNS development through a lineage-specific transcription factor that together with the kernel gene creates cis-regulatory input that contributes to transcriptionally activate a battery of terminal differentiation genes.

Vyšlo v časopise: PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004360
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004360

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