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

Pillay, L.M., Forrester, A.M., Erickson, T., Berman, J.N., and Waskiewicz, A.J.
Developmental Biology   340(2): 306-317 (Journal)
Registered Authors
Berman, Jason, Forrester, Michael, Waskiewicz, Andrew
Pbx, Meis, Meis1, Gata1, Hematopoiesis, Zebrafish, Hox, Hoxb7a, Cdx, Lmo2, Hemoglobin, Scl, Erythropoiesis, Erythroid, Myeloid, Myelopoiesis, Pu.1, Spi1
MeSH Terms
  • Animals
  • Cell Lineage/genetics
  • Embryo, Nonmammalian
  • Erythroid Precursor Cells/cytology
  • Erythropoiesis/genetics
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis/genetics*
  • Histocytochemistry
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Homeodomain Proteins/physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Myelopoiesis/genetics
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism
  • Neoplasm Proteins/physiology*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcription Factors/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
20123093 Full text @ Dev. Biol.
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
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes