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The transcription factors Scl and Lmo2 are crucial for development of all blood. An important early requirement for Scl in endothelial development has also been revealed recently in zebrafish embryos, supporting previous findings in scl(-/-) embryoid bodies. Scl depletion culminates most notably in failure of dorsal aorta formation, potentially revealing a role in the formation of hemogenic endothelium. We now present evidence that the requirements for Lmo2 in zebrafish embryos are essentially the same as for Scl. The expression of important hematopoietic regulators is lost, reduced, or delayed, panendothelial gene expression is down-regulated, and aorta-specific marker expression is lost. The close similarity of the phenotypes for Scl and Lmo2 suggest that they perform these early functions in hemangioblast development within a multiprotein complex, as shown for erythropoiesis. Consistent with this, we find that scl morphants cannot be rescued by a non-Lmo2-binding form of Scl but can be rescued by non-DNA-binding forms, suggesting tethering to target genes through DNA-binding partners linked via Lmo2. Interestingly, unlike other hematopoietic regulators, the Scl/Lmo2 complex does not appear to autoregulate, as neither gene's expression is affected by depletion of the other. Thus, expression of these critical regulators is dependent on continued expression of upstream regulators, which may include cell-extrinsic signals.

Original publication

DOI

10.1182/blood-2006-02-003087

Type

Journal article

Journal

Blood

Publication Date

15/03/2007

Volume

109

Pages

2389 - 2398

Keywords

Adaptor Proteins, Signal Transducing, Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Line, DNA, DNA-Binding Proteins, Embryo, Nonmammalian, Endothelial Cells, Erythroid Cells, Gene Expression Regulation, Developmental, Hematopoiesis, Hematopoietic Stem Cells, LIM Domain Proteins, Metalloproteins, Mice, Myeloid Cells, Phenotype, Protein Binding, Proto-Oncogene Proteins, Transcription Factors, Zebrafish, Zebrafish Proteins