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 Anthony Lutty, Heinz Arnheiter, Ruth Ashery-Padan

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article numbere1004360
JournalPLoS Genetics
Volume10
Issue number5
DOIs
StatePublished - 2014

Fingerprint

melanogenesis
epithelium
Epithelium
gene
somatic mutation
Organogenesis
Gene Regulatory Networks
nervous system
organogenesis
pancreas
Mutagenesis
central nervous system
pigment
Pancreas
Protein Isoforms
Central Nervous System
eyes
pigments
cells
Gene Expression

ASJC Scopus subject areas

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

Cite this

Raviv, S., Bharti, K., Rencus-Lazar, S., Cohen-Tayar, Y., Schyr, R., Evantal, N., ... Ashery-Padan, R. (2014). PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF. PLoS Genetics, 10(5), [e1004360]. https://doi.org/10.1371/journal.pgen.1004360

PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF. / Raviv, Shaul; Bharti, Kapil; Rencus-Lazar, Sigal; Cohen-Tayar, Yamit; Schyr, Rachel; Evantal, Naveh; Meshorer, Eran; Zilberberg, Alona; Idelson, Maria; Reubinoff, Benjamin; Grebe, Rhonda; Rosin-Arbesfeld, Rina; Lauderdale, James; Lutty, Gerard Anthony; Arnheiter, Heinz; Ashery-Padan, Ruth.

In: PLoS Genetics, Vol. 10, No. 5, e1004360, 2014.

Research output: Contribution to journalArticle

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, GA, 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
Raviv, Shaul ; Bharti, Kapil ; Rencus-Lazar, Sigal ; Cohen-Tayar, Yamit ; Schyr, Rachel ; Evantal, Naveh ; Meshorer, Eran ; Zilberberg, Alona ; Idelson, Maria ; Reubinoff, Benjamin ; Grebe, Rhonda ; Rosin-Arbesfeld, Rina ; Lauderdale, James ; Lutty, Gerard Anthony ; Arnheiter, Heinz ; Ashery-Padan, Ruth. / PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF. In: PLoS Genetics. 2014 ; Vol. 10, No. 5.
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