title: Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1.
abstract: Notch1 signaling drives T cell development at the expense of B cell development from a common precursor, an effect that is dependent on a C-terminal Notch1 transcriptional activation domain. The function of Deltex1, initially identified as a positive modulator of Notch function in a genetic screen in Drosophila, is poorly understood. We now demonstrate that, in contrast to Notch1, enforced expression of Deltex1 in hematopoietic progenitors results in B cell development at the expense of T cell development in fetal thymic organ culture and in vivo. Consistent with these effects, Deltex1 antagonizes Notch1 signaling in transcriptional reporter assays by inhibiting coactivator recruitment. These data suggest that a balance of inductive Notch1 signals and inhibitory signals mediated through Deltex1 and other modulators regulate T-B lineage commitment.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Izon
authors.forename: Jon C
authors.initials: JC
authors.lastname: Aster
authors.forename: Yiping
authors.initials: Y
authors.lastname: He
authors.forename: Andrew
authors.initials: A
authors.lastname: Weng
authors.forename: Fredrick G
authors.initials: FG
authors.lastname: Karnell
authors.forename: Vytas
authors.initials: V
authors.lastname: Patriub
authors.forename: Lanwei
authors.initials: L
authors.lastname: Xu
authors.forename: Sonia
authors.initials: S
authors.lastname: Bakkour
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez
authors.forename: David
authors.initials: D
authors.lastname: Allman
authors.forename: Warren S
authors.initials: WS
authors.lastname: Pear
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D051792:Basic Helix-Loop-Helix Proteins; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D019070:Cell Lineage; D004268:DNA-Binding Proteins; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D008214:Lymphocytes / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; C407909:TCF3 protein, human; C409218:deltex protein, vertebrate