Abstract
The helix-loop-helix protein, E47, is essential for both B- and T-lineage development. Here we demonstrate that in vitro E47 and Notch signaling act in concert to promote T cell development from fetal hematopoietic progenitors and to restrain development into the natural killer and myeloid cell lineages. The expression of an ensemble of genes associated with Notch signaling is activated by E47, and additionally, Notch signaling and E47 act in parallel pathways to induce a T lineage-specific program of gene expression. Enforced expression of the intracellular domain of Notch rescues the developmental arrest at the T cell commitment stage in E2A-deficient fetal thymocytes. Finally, we demonstrate that regulation of Hes1 expression by Notch signaling and E47 is strikingly similar to that observed during Drosophila melanogaster sensory development. Based on these observations, we propose that in developing fetal thymocytes E47 acts to induce the expression of an ensemble of genes involved in Notch signaling, and that subsequently E47 acts in parallel with Notch signaling to promote T-lineage maturation.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
B-Lymphocytes / cytology
-
B-Lymphocytes / physiology
-
Basic Helix-Loop-Helix Transcription Factors / biosynthesis
-
Cell Differentiation / physiology*
-
Cell Lineage / physiology*
-
Drosophila melanogaster
-
Fetus / cytology
-
Fetus / embryology
-
Gene Expression Regulation, Developmental / physiology
-
Hematopoietic Stem Cells / cytology
-
Hematopoietic Stem Cells / physiology*
-
Homeodomain Proteins / biosynthesis
-
Killer Cells, Natural / cytology
-
Killer Cells, Natural / physiology
-
Lymphopoiesis / physiology
-
Mice
-
Mice, Knockout
-
Receptors, Notch / metabolism
-
Signal Transduction / physiology*
-
T-Lymphocytes / cytology
-
T-Lymphocytes / physiology*
-
TCF Transcription Factors / deficiency
-
TCF Transcription Factors / metabolism
-
Thymus Gland / cytology
-
Thymus Gland / embryology*
-
Transcription Factor 7-Like 1 Protein
-
Transcription Factor HES-1
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
Hes1 protein, mouse
-
Homeodomain Proteins
-
Receptors, Notch
-
TCF Transcription Factors
-
Tcf7l1 protein, mouse
-
Transcription Factor 7-Like 1 Protein
-
Transcription Factor HES-1