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Development. 2019 May 22;146(10). pii: dev173112. doi: 10.1242/dev.173112.

Barhl2 maintains T cell factors as repressors and thereby switches off the Wnt/β-Catenin response driving Spemann organizer formation.

Author information

1
Institut Curie, Research Division, PSL Research University, Université Paris Sud, CNRS UMR 3347, INSERM U1021, Centre Universitaire, Bâtiment 110, Orsay Cedex F-91405, France.
2
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris Sud, Université Paris-Saclay, 91405 Orsay 91405, France.
3
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, S1.7 CNRS 8197, INSERM U1024 46 rue d'Ulm 75005, Paris F-75005, France.
4
Institut Curie, PSL Research University, CNRS, UMR3664, Equipe Labellisée Ligue contre le Cancer, Paris 75005, France.
5
Institut Curie, Research Division, PSL Research University, Université Paris Sud, CNRS UMR 3347, INSERM U1021, Centre Universitaire, Bâtiment 110, Orsay Cedex F-91405, France beatrice.durand@curie.fr beatrice.durand@sorbonne-universite.fr.

Abstract

A hallmark of Wnt/β-Catenin signaling is the extreme diversity of its transcriptional response, which varies depending on the cell and developmental context. What controls this diversity is poorly understood. In all cases, the switch from transcriptional repression to activation depends on a nuclear increase in β-Catenin, which detaches the transcription factor T cell factor 7 like 1 (Tcf7l1) bound to Groucho (Gro) transcriptional co-repressors from its DNA-binding sites and transiently converts Tcf7/Lymphoid enhancer binding factor 1 (Lef1) into a transcriptional activator. One of the earliest and evolutionarily conserved functions of Wnt/β-Catenin signaling is the induction of the blastopore lip organizer. Here, we demonstrate that the evolutionarily conserved BarH-like homeobox-2 (Barhl2) protein stabilizes the Tcf7l1-Gro complex and maintains the repressed expression of Tcf target genes by a mechanism that depends on histone deacetylase 1 (Hdac-1) activity. In this way, Barhl2 switches off the Wnt/β-Catenin-dependent early transcriptional response, thereby limiting the formation of the organizer in time and/or space. This study reveals a novel nuclear inhibitory mechanism of Wnt/Tcf signaling that switches off organizer fate determination.

KEYWORDS:

Barhl2; Groucho/Tle; Hdac; Organizer; Pluripotency; Stem cells; Tcf/Lef; Transcription; Wnt

PMID:
31036545
DOI:
10.1242/dev.173112

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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