GATA-2 functions downstream of BMPs and CaM KIV in ectodermal cells during primitive hematopoiesis.
In Xenopus, primitive blood originates from the mesoderm, but extrinsic signals from the ectoderm are required during gastrulation to enable these cells to differentiate as erythrocytes. The nature of these signals, and how they are transcriptionally regulated, is not well understood. We have previously shown that bone morphogenetic proteins (BMPs) are required to signal to ectodermal cells to generate secondary non-cell-autonomous signal(s) necessary for primitive erythropoiesis, and that calmodulin-dependent protein kinase IV (CaM KIV) antagonizes BMP signaling. The current studies demonstrate that Gata-2 functions downstream of BMP receptor activation in these same cells, and is a direct target for antagonism by CaM KIV. We show, using loss of function analysis in whole embryos and in explants, that ectodermal Gata-2 is required for primitive erythropoiesis, and that BMP signals cannot rescue blood defects caused by ectoderm removal or loss of ectodermal GATA-2. Furthermore, we provide evidence that acetylation of GATA-2 is required for its function in primitive blood formation in vivo. Our data support a model in which Gata-2 is a transcriptional target downstream of BMPs within ectodermal cells, while activation of the CaM KIV signaling pathway alters GATA-2 function posttranslationally, by inhibiting its acetylation.
Dalgin
Gokhan
G
Department of Cell and Developmental Biology, Oregon Health and Science University, School of Medicine, Portland, OR 97239-3098, USA.
Goldman
Devorah C
DC
Donley
Nathan
N
Ahmed
Riffat
R
Eide
Christopher A
CA
Christian
Jan L
JL
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000502:physiology*; D004475:Ectoderm / Q000502:physiology; D004920:Erythropoiesis; D005260:Female; D050989:GATA2 Transcription Factor / Q000502:physiology*; D006410:Hematopoiesis; D014981:Xenopus / Q000196:embryology / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D050989:GATA2 Transcription Factor; C494714:GATA2 protein, Xenopus; D029867:Xenopus Proteins; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4