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

Shaul Raviv; Kapil Bharti; Sigal Rencus-Lazar; Yamit Cohen-Tayar; Rachel Schyr; Naveh Evantal; Eran Meshorer; Alona Zilberberg; Maria Idelson; Benjamin Reubinoff; Rhonda Grebe; Rina Rosin-Arbesfeld; James Lauderdale; Gerard Lutty; Heinz Arnheiter; Ruth Ashery-Padan

doi:10.1371/journal.pgen.1004360

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

Shaul Raviv, Kapil Bharti, Sigal Rencus-Lazar, Yamit Cohen-Tayar, Rachel Schyr, Naveh Evantal, Eran Meshorer, Alona Zilberberg, Maria Idelson, Benjamin Reubinoff, Rhonda Grebe, Rina Rosin-Arbesfeld, James Lauderdale, Gerard Lutty, Heinz Arnheiter, Ruth Ashery-Padan

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, we aimed to determine the roles and the hierarchical organization of the PAX6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF during onset of melanogenesis. PAX6 both controls the expression of an RPE isoform of Mitf and synergizes with MITF to activate expression of genes involved in pigment biogenesis. This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage.

Original language	English (US)
Article number	e1004360
Journal	PLoS genetics
Volume	10
Issue number	5
DOIs	https://doi.org/10.1371/journal.pgen.1004360
State	Published - May 2014
Externally published	Yes

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Raviv, S., Bharti, K., Rencus-Lazar, S., Cohen-Tayar, Y., Schyr, R., Evantal, N., Meshorer, E., Zilberberg, A., Idelson, M., Reubinoff, B., Grebe, R., Rosin-Arbesfeld, R., Lauderdale, J., Lutty, G., Arnheiter, H., & Ashery-Padan, R. (2014). PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF. PLoS genetics, 10(5), Article e1004360. https://doi.org/10.1371/journal.pgen.1004360

Raviv, S, Bharti, K, Rencus-Lazar, S, Cohen-Tayar, Y, Schyr, R, Evantal, N, Meshorer, E, Zilberberg, A, Idelson, M, Reubinoff, B, Grebe, R, Rosin-Arbesfeld, R, Lauderdale, J, Lutty, G, Arnheiter, H & Ashery-Padan, R 2014, 'PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF', PLoS genetics, vol. 10, no. 5, e1004360. https://doi.org/10.1371/journal.pgen.1004360

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abstract = "During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, we aimed to determine the roles and the hierarchical organization of the PAX6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF during onset of melanogenesis. PAX6 both controls the expression of an RPE isoform of Mitf and synergizes with MITF to activate expression of genes involved in pigment biogenesis. This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage.",

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AU - Schyr, Rachel

AU - Evantal, Naveh

AU - Meshorer, Eran

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AU - Idelson, Maria

AU - Reubinoff, Benjamin

AU - Grebe, Rhonda

AU - Rosin-Arbesfeld, Rina

AU - Lauderdale, James

AU - Lutty, Gerard

AU - Arnheiter, Heinz

AU - Ashery-Padan, Ruth

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

Abstract

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