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XB-ART-51246
Dev Biol November 1, 2015; 407 (1): 1-11.

GATA2 regulates Wnt signaling to promote primitive red blood cell fate.

Mimoto MS , Kwon S , Green YS , Goldman D , Christian JL .


Abstract
Primitive erythropoiesis is regulated in a non cell-autonomous fashion across evolution from frogs to mammals. In Xenopus laevis, signals from the overlying ectoderm are required to induce the mesoderm to adopt an erythroid fate. Previous studies in our lab identified the transcription factor GATA2 as a key regulator of this ectodermal signal. To identify GATA2 target genes in the ectoderm required for red blood cell formation in the mesoderm, we used microarray analysis to compare gene expression in ectoderm from GATA2 depleted and wild type embryos. Our analysis identified components of the non-canonical and canonical Wnt pathways as being reciprocally up- and down-regulated downstream of GATA2 in both mesoderm and ectoderm. We show that up-regulation of canonical Wnt signaling during gastrulation blocks commitment to a hematopoietic fate while down-regulation of non-canonical Wnt signaling impairs erythroid differentiation. Our results are consistent with a model in which GATA2 contributes to inhibition of canonical Wnt signaling, thereby permitting progenitors to exit the cell cycle and commit to a hematopoietic fate. Subsequently, activation of non-canonical Wnt signaling plays a later role in enabling these progenitors to differentiate as mature red blood cells.

PubMed ID: 26365900
PMC ID: PMC4641806
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: axin2 bmp2 bmp4 bmp7.1 ephb2 ets1 fzd4 fzd7 fzd8 gata2 hba3 myb tal1 wnt11 wnt4 wnt5a wnt8a zfpm1
Morpholinos: gata2 MO1 gata2 MO2

Phenotypes: Xla Wt + LiCl (fig.S4) [+]

Article Images: [+] show captions
References [+] :
Afouda, Different requirements for GATA factors in cardiogenesis are mediated by non-canonical Wnt signaling. 2011, Pubmed, Xenbase