Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1.
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.
Izon
David J
DJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Aster
Jon C
JC
He
Yiping
Y
Weng
Andrew
A
Karnell
Fredrick G
FG
Patriub
Vytas
V
Xu
Lanwei
L
Bakkour
Sonia
S
Rodriguez
Carlos
C
Allman
David
D
Pear
Warren S
WS
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
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