Developmental Genomics of T-Cell Transcription Factors

California Institute Of Technology, Pasadena CA

Investigators

Abstract

E. Rothenberg; MCB 9983129 Abstract This research employs a genomics-based strategy to identify new transcription factors that help regulate the complex choice of blood-cell precursors that develop into T lymphocytes. The method allows candidate regulatory genes to be characterized even when classical genetic screens are impossible and the important regulatory target genes are unknown. The basic resources for the project are arrayed cDNA libraries from cells in the process of making this choice, prepared from the developmentally-arrested lymphocytes of mutant mice. These libraries are initially screened to identify clones likely to encode transcription factors. A broad screening method is then used that detects the presence of domains conserved in various transcription factor families, enabling members of over a score of different factor classes to be identified. The whole ensemble of putative transcription factor clones will then be characterized to determine their expression in the early choice points in T lymphocyte development. A subset of the clones with particularly interesting expression patterns will then be analyzed in detail for structure and for developmental regulation at a fine scale. Important tools used for this project will be the rich array of cell population markers for mouse lymphocytes and the availability of mutants that block the process at known points, allowing a stage-by- stage dissection of the T-cell developmental pathway. This system is a richly informative model for studying how the generation of particular cell types from multipotent precursors can be regulated.