TY - JOUR
T1 - PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF
AU - Raviv, Shaul
AU - Bharti, Kapil
AU - Rencus-Lazar, Sigal
AU - Cohen-Tayar, Yamit
AU - Schyr, Rachel
AU - Evantal, Naveh
AU - Meshorer, Eran
AU - Zilberberg, Alona
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
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84901645731&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1004360
DO - 10.1371/journal.pgen.1004360
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AN - SCOPUS:84901645731
SN - 1553-7390
VL - 10
JO - PLoS Genetics
JF - PLoS Genetics
IS - 5
M1 - e1004360
ER -