Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1

David J Izon; Jon C Aster; Yiping He; Andrew Weng; Fredrick G Karnell; Vytas Patriub; Lanwei Xu; Sonia Bakkour; Carlos Rodriguez; David Allman; Warren S Pear

doi:10.1016/s1074-7613(02)00271-6

Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1

Immunity. 2002 Feb;16(2):231-43. doi: 10.1016/s1074-7613(02)00271-6.

Authors

David J Izon¹, Jon C Aster, Yiping He, Andrew Weng, Fredrick G Karnell, Vytas Patriub, Lanwei Xu, Sonia Bakkour, Carlos Rodriguez, David Allman, Warren S Pear

Affiliation

¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.

PMID: 11869684
DOI: 10.1016/s1074-7613(02)00271-6

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

3T3 Cells
Animals
B-Lymphocytes / cytology*
Basic Helix-Loop-Helix Transcription Factors
Bone Marrow Cells / cytology
Carrier Proteins*
Cell Differentiation
Cell Line, Transformed
Cell Lineage
DNA-Binding Proteins*
Gene Expression
Hematopoietic Stem Cells / cytology*
Humans
Liver / cytology
Liver / embryology
Lymphocytes / cytology
Membrane Proteins / metabolism*
Mice
Organ Culture Techniques
Protein Biosynthesis*
Proteins / genetics
Receptor, Notch1
Receptors, Cell Surface*
Recombinant Fusion Proteins / biosynthesis
Recombinant Fusion Proteins / genetics
Signal Transduction*
T-Lymphocytes / cytology*
Thymus Gland / cytology
Thymus Gland / embryology
Transcription Factors / metabolism
Transcriptional Activation
Tumor Cells, Cultured

Substances

Basic Helix-Loop-Helix Transcription Factors
Carrier Proteins
DNA-Binding Proteins
Membrane Proteins
NOTCH1 protein, human
Notch1 protein, mouse
Proteins
Receptor, Notch1
Receptors, Cell Surface
Recombinant Fusion Proteins
TCF3 protein, human
Transcription Factors
deltex protein, vertebrate