Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment
Flt3Abstract
Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and the activity of a number of transcription factors. One factor, Pax5, is required for commitment to the B-cell lineage, although the molecular mechanism by which this occurs is unknown. We demonstrate here that an important function of Pax5 is to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the reintroduction of Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development. These findings demonstrate that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.
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↵1 Corresponding author.
↵1 E-MAIL nutt{at}wehi.edu.au; FAX 61-3-9347-0852.
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1396206
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- Received November 28, 2005.
- Accepted February 8, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press