Lineage commitment in lymphopoiesis.
The mechanisms controlling the commitment of hematopoietic progenitor cells to the lymphoid lineages are still mostly unknown. Recent findings indicate that the earliest phase of B cell development may proceed in two steps. At the onset of B-lymphopoiesis, the transcription factors E2A and EBF coordinately activate the B-cell-specific gene expression program. Subsequently, Pax5 appears to repress the promiscuous transcription of lineage-inappropriate genes and thus commits progenitor cells to the B-lymphoid pathway by suppressing alternative cell fates. B-lineage commitment by Pax5 seems to occur in a stochastic manner in the bone marrow, as indicated by the random activation of only one of the two Pax5 alleles in early pro-B cells. In contrast, loss- and gain-of-function analyses have implicated the Notch1 receptor in the specification of the T cell fate, which may thus be controlled by instructive signals in the thymus.
Busslinger
M
M
Research Institute of Molecular Pathology, Vienna, A-1030, Austria. busslinger@nt.imp.univie.ac.at
Nutt
S L
SL
Rolink
A G
AG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051757:PAX5 Transcription Factor; D010641:Phenotype; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D013269:Stochastic Processes; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; C081976:EBF1 protein, human; C489921:Ebf1 protein, mouse; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; C407909:TCF3 protein, human