How Gene Regulatory Networks Connect to Development

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Many model systems study early development of animals with the goal to understand the normal mechanisms of morphogenesis. This is important because early in development the cells of the embryo exhibit a series of dramatic cell rearrangements that establish the primitive body plan of the animal. This complex sequence is quite robust yet is thought to t)e the source of many unexplained human birth defects. A number of approaches have attempted to understand and reduce those defects, but perhaps the best research direction in the long run is to thoroughly understand how embryos normally transect these early developmental stages. In this project the goal is to understand in a model system, the sea urchin, how the earliest gene regulatory network controls cellular processes that contribute to morphogenesis, patterning and reprogramming. The control machinery of development are the transcriptional networks that regulate all cellular activities. Among the best-understood gene regulatory networks (GRNs) is the one that governs specification of early sea urchin development up to the beginning of gastrulation. This project will take advantage of that knowledge to examine how the next steps of development are controlled. The idea is that sub-circuits of the endomesoderm GRN control "morphoregulator" molecule expression, and these in turn control the cell biological processes that conduct morphogenetic movements, pattern the skeleton, and control a capacity for cellular reprogramming in the embryo. Three specific aims will be pursued. The first will be to use the GRN, transcriptomes, gene candidate lists, and perturbations to identify the morphoregulators that control the several phases of archenteron invagination. The second aim will be to examine how the GRN controls release of signals from the ectoderm in such a precise manner that enables the skeletogenic cells to produce a correctly patterned skeleton. The third aim will examine how the state of the GRN is able to shift as it reprograms. There the goal will be to identify a repressor of reprogramming, and also to record the state changes as the GRN shifts from one specification state to another. Each of these aims draws upon the advanced state of understanding of the sea urchin gene regulatory network.