| First Author | Medina KL | Year | 2004 |
| Journal | Dev Cell | Volume | 7 |
| Issue | 4 | Pages | 607-17 |
| PubMed ID | 15469848 | Mgi Jnum | J:106498 |
| Mgi Id | MGI:3618665 | Doi | 10.1016/j.devcel.2004.08.006 |
| Citation | Medina KL, et al. (2004) Assembling a gene regulatory network for specification of the B cell fate. Dev Cell 7(4):607-17 |
| abstractText | The generation of B lymphocyte precursors is dependent on the combinatorial action of the transcription factors PU.1, Ikaros, E2A, EBF, and Pax-5. Loss of PU.1 results in a severe reduction in Flk2+, IL-7R+ lymphoid progenitors as well as impaired expression of EBF and Pax-5. Restoration of EBF expression facilitates rapid generation of pro-B cells from PU.1-/- progenitors. Molecular analysis suggests that PU.1 directly participates in regulation of the EBF gene. Although PU.1 is dispensable for expression of most early B lineage genes, it is required for CD45R/B220. Using EBF-/- mutant progenitors, we show that EBF induces Pax-5 and the early program of B lineage gene expression. Importantly, Pax-5 does not rescue B cell development from either PU.1-/- or EBF-/- progenitors. Pax-5 expression and function are contingent on EBF. Based on these results, we propose a hierarchical regulatory network for specification and commitment to the B cell fate. |
