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PMID: 12569129 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse.

Genes & development ·Vol. 17 ·No. 3 ·2003-02-01 ·Pages 380-93

Ema M, Faloon P, Zhang WJ, Hirashima M, Reid T, Stanford WL, Orkin S, Choi K, Rossant J

Abstract

Mouse embryos mutant for the VEGF receptor, VEGFR2, Flk-1, or Kdr, fail to form both endothelial and hematopoietic cells, suggesting a possible role in a common progenitor to both lineages. The transcription factor Tal1 (Scl), is not expressed in Flk1(-/-) embryos, consistent with a downstream role in the Flk1 pathway. We tested whether expression of Tal1 under the Flk1 promoter was sufficient to rescue the loss of endothelial and hematopoietic cells in Flk1 mutants. Only partial rescue of hematopoiesis and endothelial development was observed in vivo. However, Flk1(-/Tal1) embryonic stem (ES) cells were capable of blast colony formation in vitro at levels equivalent to Flk1(+/-) heterozygotes. Ectopic expression of Tal1 under the Flk1 promoter in Flk1(+/-) mouse embryos or ES cells caused no obvious pathology but increased the number of blast colony forming cells (BL-CFCs) and enhanced their hematopoietic potential. These single-cell-derived BL-CFCs also produced smooth muscle cells in vitro. Increased Tal1 expression inhibited smooth muscle differentiation in this assay, whereas loss of Tal1 promoted smooth muscle formation. We propose a model in which the combinatorial effects of Flk1 and Tal1 act to regulate cell fate choice in early development into hematopoietic, endothelial, and smooth muscle lineages.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Cardiovascular System/embryology Cell Differentiation/physiology DNA-Binding Proteins/metabolism Endothelium/physiology Hematopoiesis/physiology Mice Proto-Oncogene Proteins/metabolism Stem Cells T-Cell Acute Lymphocytic Leukemia Protein 1 Transcription Factors/metabolism Vascular Endothelial Growth Factor Receptor-2/metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins Proto-Oncogene Proteins T-Cell Acute Lymphocytic Leukemia Protein 1 Tal1 protein, mouse Transcription Factors Vascular Endothelial Growth Factor Receptor-2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ema Masatsugu
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5.
Faloon Patrick
Zhang Wen Jie
Hirashima Masanori
Reid Tammy
Stanford William L
Orkin Stuart
Choi Kyunghee
Rossant Janet
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1049803
Published
2003-02-01
Pages
380-93
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC195986
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1049803 PMC Full Text View journal details
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