GATA2 regulates Wnt signaling to promote primitive red blood cell fate

Mizuho S. Mimoto, Sunjong Kwon, Yangsook Song Green, Devorah Goldman, Jan L. Christian

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalDevelopmental Biology
Volume407
Issue number1
DOIs
StatePublished - Nov 1 2015

Fingerprint

Ectoderm
Mesoderm
Erythrocytes
GATA2 Transcription Factor
Gastrulation
Wnt Signaling Pathway
Erythropoiesis
Xenopus laevis
Microarray Analysis
Anura
Mammals
Cell Cycle
Up-Regulation
Down-Regulation
Embryonic Structures
Gene Expression
Genes

Keywords

  • GATA2
  • Non cell-autonomous signals
  • Primitive hematopoiesis
  • Wnt
  • Xenopus laevis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

GATA2 regulates Wnt signaling to promote primitive red blood cell fate. / Mimoto, Mizuho S.; Kwon, Sunjong; Green, Yangsook Song; Goldman, Devorah; Christian, Jan L.

In: Developmental Biology, Vol. 407, No. 1, 01.11.2015, p. 1-11.

Research output: Contribution to journalArticle

Mimoto, Mizuho S. ; Kwon, Sunjong ; Green, Yangsook Song ; Goldman, Devorah ; Christian, Jan L. / GATA2 regulates Wnt signaling to promote primitive red blood cell fate. In: Developmental Biology. 2015 ; Vol. 407, No. 1. pp. 1-11.
@article{2c125e40f3d244de8511f3d530b54a59,
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.",
keywords = "GATA2, Non cell-autonomous signals, Primitive hematopoiesis, Wnt, Xenopus laevis",
author = "Mimoto, {Mizuho S.} and Sunjong Kwon and Green, {Yangsook Song} and Devorah Goldman and Christian, {Jan L.}",
year = "2015",
month = "11",
day = "1",
doi = "10.1016/j.ydbio.2015.08.012",
language = "English (US)",
volume = "407",
pages = "1--11",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - GATA2 regulates Wnt signaling to promote primitive red blood cell fate

AU - Mimoto, Mizuho S.

AU - Kwon, Sunjong

AU - Green, Yangsook Song

AU - Goldman, Devorah

AU - Christian, Jan L.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - GATA2

KW - Non cell-autonomous signals

KW - Primitive hematopoiesis

KW - Wnt

KW - Xenopus laevis

UR - http://www.scopus.com/inward/record.url?scp=84947866159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947866159&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2015.08.012

DO - 10.1016/j.ydbio.2015.08.012

M3 - Article

VL - 407

SP - 1

EP - 11

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -