Insulin signaling in L1 growth and arrest
Insulin-like signaling regulates L1 arrest. Mutation of the insulin receptor daf-2 results in developmental arrest in the presence of food and extended starvation survival in its absence. In contrast, mutation of the FOXO transcription factor daf-16, which is a downstream effector of insulin signaling, results in an arrest-defective phenotype that includes post-embryonic development and death in the absence of food.
However, the C. elegans genome encodes 40 insulin-like ligands comprising a complex signaling network with multiple levels of feedback potentially operating within and between tissues. Chemosensory neurons and intestinal cells both contribute to systemic regulation via nutritionally regulated transcription and secretion of insulin ligands. Our working model is that this signaling network coordinates growth, development and metabolism so that coherent physiological states are maintained across the animal as it responds to varying environmental conditions.
We are using expression analysis to infer sites and dynamics of insulin expression, and we are using genetic techniques to examine insulin gene function. Given an effect on organismal phenotype, we have cell-based phenotypes to tease apart network function in the context of multi-cellular development. We seek to identify insulin ligands whose function can account for the L1 arrest phenotypes observed with daf-2 and daf-16 mutants and to develop a model for the organismal signaling network they comprise.