Instructions for building tissues and organs are encoded into the genome and at each Step of embryonic development a series of transcriptional regulatory events are required for their accurate execution. Understanding the regulatory programs that pattern genes during embryogenesis is a key step in understanding developmental diseases and the mechanisms behind the formation and repair of healthy tissues and organs. The mechanisms that pattern tissues and organs are strikingly similar across species. Therefore model organisms, like the fruit fly, provide convenient experimental systems to explore the basic principles that guide tissue morphogenesis. Despite the availability of numerous genomes and techniques to physically map transcription factor binding site locations and chromatin states, the regulatory programs implemented during tissue and organ development are challenging to assemble. A critical barrier is the incorporation of spatial and temporal gene expression data into the construction and analysis of regulatory networks. In this proposal, spatial and temporal expression pattern data will be integrated with a range of heterogeneous datasets in order to assemble and analyze developmental gene regulatory connections.
The first aim of the proposal is to develop a language for the assembly of geometric models to represent gene expression patterns using a combination of simple shapes (primitives) and Boolean operations. In parallel, regulatory regions within the genome will be predicted using a combination of sequence, transcription factor binding locations, and chromatin states.
The final aim of the proposal investigates connections between regulatory grammar and spatial expression domains. These approaches will be developed using spatial expression patterns for over 4000 genes patterned during Drosophila melanogaster embryogenesis and will be central to interpreting the datasets generated in the modENCODE project in the context of tissue and organ development. Relevance to public health: Studying the mechanisms by which healthy tissues and organs are patterned is central to understanding developmental disease and will provide important insight into how adult tissues can be repaired or organs can be engineered for transplantation. Examining tissue and organ development in model organisms, like the fruit fly, is directly relevant to human health, as many of the mechanisms that pattern tissues in a model organism are same in humans.
