Developmental Buffering in a Gene Regulatory Network

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In living systems, noise in gene expression can lead to differences in phenotype, even among genetically identical cells. This project will study the basis for different phenotypes occurring in animals carrying the same genotype, using the development of the gut in the nematode C. elegans as a model. The genetic pathway controlling specification of the gut involves transient activation of the genes end-1 and end-3. Mutated versions of these genes have been introduced into C. elegans animals that lack the normal copies. Preliminary results show that only some embryos make gut, and that surviving adults have abnormal guts. This project will study the basis for these effects. First, the development of the gut in end mutant embryos will be examined at high resolution. Second, global gene expression in adult guts will be compared with normal animals, and possible defects in function of genes in the gut specification pathway will be tested. Third, sources of noise in the upstream-most components of gut specification will be measured, and genes whose products influence the stochastic specification of gut will be identified. Reverse genetics (using RNA interference), time lapse microscopy, and high-throughput sequencing of expressed genes (RNA-Seq) will be used. The experiments will describe gut development at high resolution in a new set of mutants, characterize defects in adult intestines derived from the mutant strains, and identify possible sources of gene expression noise in organ specification. The work has the potential to define new paradigms for how living systems manage inherent differences in gene expression during development. In the course of performing this work, the PI, himself of Hispanic descent, will train undergraduates from the diverse UC Riverside campus, and a graduate student. A laboratory course for first-year Biology undergraduates will train students in research and allow them to carry out original research.