title: GATA2 regulates Wnt signaling to promote primitive red blood cell fate.
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.
authors.affiliation: Department of Cell and Developmental Biology Oregon Health and Science University, School of Medicine, Portland, OR 97239-3098, USA.
authors.forename: Mizuho S
authors.initials: MS
authors.lastname: Mimoto
authors.affiliation: Department of Cell and Developmental Biology Oregon Health and Science University, School of Medicine, Portland, OR 97239-3098, USA.
authors.forename: Sunjong
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies University of Utah, School of Medicine, Salt Lake City, UT 94132, USA.
authors.forename: Yangsook Song
authors.initials: YS
authors.lastname: Green
authors.affiliation: Department of Cell and Developmental Biology Oregon Health and Science University, School of Medicine, Portland, OR 97239-3098, USA.
authors.forename: Devorah
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Department of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies University of Utah, School of Medicine, Salt Lake City, UT 94132, USA. Electronic address: jan.christian@neuro.utah.edu.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Christian
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000032:analysis; D019070:Cell Lineage; D004920:Erythropoiesis; D050989:GATA2 Transcription Factor / Q000502:physiology*; D054262:Gastrulation; D060449:Wnt Signaling Pathway / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D050989:GATA2 Transcription Factor; C494714:GATA2 protein, Xenopus; D029867:Xenopus Proteins
keywords: GATA2; Non cell-autonomous signals; Primitive hematopoiesis; Wnt; Xenopus laevis