PUBLICATION

The Hox cofactors Meis1 and Pbx act upstream of gata1 to regulate primitive hematopoiesis

Authors

Pillay, L.M., Forrester, A.M., Erickson, T., Berman, J.N., and Waskiewicz, A.J.

ID

ZDB-PUB-100211-7

Date

2010

Source

Developmental Biology 340(2): 306-317 (Journal)

Registered Authors

Berman, Jason, Forrester, Michael, Waskiewicz, Andrew

Keywords

Pbx, Meis, Meis1, Gata1, Hematopoiesis, Zebrafish, Hox, Hoxb7a, Cdx, Lmo2, Hemoglobin, Scl, Erythropoiesis, Erythroid, Myeloid, Myelopoiesis, Pu.1, Spi1

MeSH Terms

Myelopoiesis/genetics
Neoplasm Proteins/genetics
Neoplasm Proteins/metabolism
Neoplasm Proteins/physiology*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Zebrafish Proteins/physiology*
Embryo, Nonmammalian
Histocytochemistry
Zebrafish/embryology
Zebrafish/genetics
Zebrafish/metabolism
Erythroid Precursor Cells/cytology
Animals
GATA1 Transcription Factor/genetics
GATA1 Transcription Factor/metabolism
Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism
Homeodomain Proteins/physiology*
Hematopoiesis/genetics*
Immunohistochemistry
Cell Lineage/genetics
Erythropoiesis/genetics
Transcription Factors/genetics
Transcription Factors/metabolism
Transcription Factors/physiology*
In Situ Hybridization
Gene Expression Regulation, Developmental*

PubMed

20123093 Full text @ Dev. Biol.

Abstract

During vertebrate development, the initial wave of hematopoiesis produces cells that help to shape the developing circulatory system and oxygenate the early embryo. The differentiation of primitive erythroid and myeloid cells occurs within a short transitory period, and is subject to precise molecular regulation by a hierarchical cascade of transcription factors. The TALE-class homeodomain transcription factors Meis and Pbx function to regulate embryonic hematopoiesis, but it is not known where Meis and Pbx proteins participate in the hematopoietic transcription factor cascade. To address these questions, we have ablated Meis1 and Pbx proteins in zebrafish, and characterized their molecular effects on known markers of primitive hematopoiesis. Embryos lacking Meis1 and Pbx exhibit a severe reduction in the expression of gata1, the earliest marker of erythroid cell fate, and fail to produce visible circulating blood cells. Concomitant with a loss of gata1, Meis1- and Pbx-depleted embryos exhibit downregulated embryonic hemoglobin (hbae3) expression, and possess increased numbers of pu.1-positive myeloid cells. gata1-overexpression rescues hbae3 expression in Pbx-depleted; meis1-morphant embryos, placing Pbx and Meis1 upstream of gata1 in the erythropoietic transcription factor hierarchy. Our study conclusively demonstrates that Meis1 and Pbx act to specify the erythropoietic cell lineage and inhibit myelopoiesis.

Genes / Markers

Figures