Many model systems study eariy development of animals with the goal to understand the normal mechanisms of morphogenesis. This is important because early in development the cells ofthe embryo exhibit a series of dramafic cell rearrangements that establish the primitive body plan ofthe 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 eariy developmental stages. In this project the goal is to understand in a model system, the sea urchin, how the eariiest 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 acfivifies. Among the best-understood gene regulatory networks (GRNs) is the one that governs specificafion 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 ofthe 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 perturbafions to identify the morphoregulators that control the several phases of archenteron invaginafion.
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 correcfiy 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 specificafion state to another. Each of these aims draws upon the advanced state of understanding of the sea urchin gene regulatory network.

Public Health Relevance

Here a well understood network of transcripfion factors and signals will be connected to the next level of control regulafing cell movements, cell patterning, and cell reprogramming, all necessary components for building a healthy organism.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Special Emphasis Panel (ZHD1-DSR-Z (ED))
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California Institute of Technology
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Warner, Jacob F; Miranda, Esther L; McClay, David R (2016) Contribution of hedgehog signaling to the establishment of left-right asymmetry in the sea urchin. Dev Biol 411:314-24
Peter, Isabelle S; Davidson, Eric H (2016) Implications of Developmental Gene Regulatory Networks Inside and Outside Developmental Biology. Curr Top Dev Biol 117:237-51
Simoes-Costa, Marcos; Bronner, Marianne E (2016) Reprogramming of avian neural crest axial identity and cell fate. Science 352:1570-3
Bronner, Marianne E (2016) How inhibitory cues can both constrain and promote cell migration. J Cell Biol 213:505-7
Uribe, Rosa A; Gu, Tiffany; Bronner, Marianne E (2016) A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system. Genesis 54:123-8
Hochgreb-Hagele, Tatiana; Koo, Daniel E S; Bronner, Marianne E (2015) Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation. Dev Biol 400:23-32
Butler, Samantha J; Bronner, Marianne E (2015) From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate. Dev Biol 398:135-46
Simões-Costa, Marcos; Stone, Michael; Bronner, Marianne E (2015) Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation. Dev Cell 34:544-54
Barriga, Elias H; Trainor, Paul A; Bronner, Marianne et al. (2015) Animal models for studying neural crest development: is the mouse different? Development 142:1555-60
Martik, Megan L; McClay, David R (2015) Deployment of a retinal determination gene network drives directed cell migration in the sea urchin embryo. Elife 4:

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