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Published April 2005 | Published
Journal Article Open

Molecular Genetics of T Cell Development

Abstract

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment.

Additional Information

"Reprinted, with permission, from the Annual Review of Fluid Mechanics, Volume 37 copyright 2005 by Annual Reviews, www.annualreviews.org" Any review like this embodies insights drawn from many people besides the authors themselves. The bibliography understates this debt. We are grateful to many colleagues for sharing their results and interpretations prior to publication, and we apologize to the many whose work we were not able to cite, or could cite only in secondary references.Work in the Rothenberg lab on transcriptional regulation of T cell development and its evolution was supported by grants from the NIH (R01 CA90233, R01 CA98925) and from NASA (NAG2-1588), with previous support from NSF (MCB-9983129) and the Stowers Institute for Medical Research.

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