Animal development requires the differentiation of the progeny ofa single cell, the zygote, into all of the cell tj^es of the organism. One way that cells distinguish themselves from other cells is through differential 1 expression of transcriptional regulatory proteins. Specific patterns of transcription factor expression in each cell can in turn regulate downstream differentiation decisions. This project focuses on defining how transcription factors pattern the increasingly complex array of cell types during the progression of development. The ultimate goal of this work is to uncover general rules through which interactions between transcription factors, chromatin modifications and other genomic features lead to appropriate regulation of downstream target genes.
We aim to generate a validated cellular resolution regulatory network of early development in the C. elegans embryo by combining genetic perturbation with in vivo resolution expression profiling. In parallel, we will test combinatorial models of transcription factor regulation of cell fate and identify direct functional targets for developmentally active transcription factors by examining the consequences of ectopic expression of each factor. When combined with other types of genomic data currently available, the results ofthese experiments will provide the basis to identify general rules governing the activity of transcription factor binding sites.
Knowledge of how transcription factors act in development can provide information about how the same transcription factors function in cancers or disease when inappropriately activated or inactivated. Furthermore, the rules governing combinatorial transcriptional regulatory logic we aim to discover should apply broadly across biology, including in disease.
|Richards, Julia L; Zacharias, Amanda L; Walton, Travis et al. (2013) A quantitative model of normal Caenorhabditis elegans embryogenesis and its disruption after stress. Dev Biol 374:12-23|