Haploinsufficiency of AML1 affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo

Immunity. 2000 Oct;13(4):423-31. doi: 10.1016/s1074-7613(00)00042-x.

Abstract

The AML1:CBFbeta transcription factor complex is essential for definitive hematopoiesis. Null mutations in mouse AML1 result in midgestational lethality with a complete lack of fetal liver hematopoiesis. While the cell autonomous nature and expression pattern of AML1 suggest an intrinsic role for this transcription factor in the developing hematopoietic system, no direct link to a functional cell type has been made. Here, we examine the consequences of AML1 loss in hematopoietic stem cells (HSC) of the mouse embryo. We demonstrate an absolute requirement for AML1 in functional HSCs. Moreover, haploinsufficiency results in a dramatic change in the temporal and spatial distribution of HSCs, leading to their early appearance in the normal position in the aorta-gonad-mesonephros region and also in the yolk sac.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / embryology
  • Aorta / transplantation
  • Cell Aggregation / genetics
  • Cell Aggregation / immunology
  • Cell Aggregation / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Colony-Forming Units Assay
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Embryo Transfer
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / physiology*
  • Female
  • Gestational Age
  • Gonads / embryology
  • Gonads / transplantation
  • Haplotypes / genetics
  • Hematopoiesis / genetics
  • Hematopoiesis / immunology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / physiology*
  • Male
  • Mesonephros / embryology
  • Mesonephros / transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Organ Culture Techniques
  • Proto-Oncogene Proteins*
  • Transcription Factors / administration & dosage
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Yolk Sac / embryology
  • Yolk Sac / transplantation

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Runx1 protein, mouse
  • Transcription Factors