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XB-ART-42715
Proc Natl Acad Sci U S A February 8, 2011; 108 (6): 2288-93.

Barhl2 limits growth of the diencephalic primordium through Caspase3 inhibition of beta-catenin activation.

Juraver-Geslin HA , Ausseil JJ , Wassef M , Durand BC .


Abstract
Little is known about the respective contributions of cell proliferation and cell death to the control of vertebrate forebrain growth. The homeodomain protein barhl2 is expressed in the diencephalons of Xenopus, zebrafish, and mouse embryos, and we previously showed that Barhl2 overexpression in Xenopus neuroepithelial cells induces Caspase3-dependent apoptosis. Here, barhl2 is shown to act as a brake on diencephalic proliferation through an unconventional function of Caspase3. Depletion of Barhl2 or Caspase3 causes an increase in diencephalic cell number, a disruption of the neuroepithelium architecture, and an increase in Wnt activity. Surprisingly, these changes are not caused by decreased apoptosis but instead, are because of an increase in the amount and activation of β-catenin, which stimulates excessive neuroepithelial cell proliferation and induces defects in β-catenin intracellular localization and an up-regulation of axin2 and cyclinD1, two downstream targets of β-catenin/T-cell factor/lymphoïd enhancer factor signaling. Using two different sets of complementation experiments, we showed that, in the developing diencephalon, Caspase3 acts downstream of Barhl2 in limiting neuroepithelial cell proliferation by inhibiting β-catenin activation. Our data argue that Bar homeodomain proteins share a conserved function as cell type-specific regulators of Caspase3 activities.

PubMed ID: 21262809
PMC ID: PMC3038765
Article link: Proc Natl Acad Sci U S A


Species referenced: Xenopus laevis
Genes referenced: acss2.2 actl6a axin2 barhl2 bcl2l1 casp3.2 cat.2 ccnd1 chrd.1 ctnnb1 endog h3-3a h4c4 khdrbs1 ncam1 otx2 shh tff3.7 wnt3a
Antibodies: Acta1 Ab5 BrdU Ab10 Casp3 Ab1 Ctnnb1 Ab1 Ctnnb1 Ab8 H3f3a Ab9 Khdrbs1 Ab1
Morpholinos: casp3 MO2 casp3.2 MO1 ctnnb1 MO1


Article Images: [+] show captions
References [+] :
Brembeck, Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. 2006, Pubmed