title: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
abstract: While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis.
authors: Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Lorin E
authors: LE
authors: Olson
authors: Jessica
authors: J
authors: Tollkuhn
authors: Claudio
authors: C
authors: Scafoglio
authors: Anna
authors: A
authors: Krones
authors: Jie
authors: J
authors: Zhang
authors: Kenneth A
authors: KA
authors: Ohgi
authors: Wei
authors: W
authors: Wu
authors: Makoto M
authors: MM
authors: Taketo
authors: Rolf
authors: R
authors: Kemler
authors: Rudolf
authors: R
authors: Grosschedl
authors: Dave
authors: D
authors: Rose
authors: Xue
authors: X
authors: Li
authors: Michael G
authors: MG
authors: Rosenfeld