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)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-Z (ED))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
California Institute of Technology
United States
Zip Code
Lyons, Deirdre C; Martik, Megan L; Saunders, Lindsay R et al. (2014) Specification to biomineralization: following a single cell type as it constructs a skeleton. Integr Comp Biol 54:723-33
Tu, Qiang; Cameron, R Andrew; Davidson, Eric H (2014) Quantitative developmental transcriptomes of the sea urchin Strongylocentrotus purpuratus. Dev Biol 385:160-7
Warner, Jacob F; McCarthy, Ali M; Morris, Robert L et al. (2014) Hedgehog signaling requires motile cilia in the sea urchin. Mol Biol Evol 31:18-22
Warner, Jacob F; McClay, David R (2014) Perturbations to the hedgehog pathway in sea urchin embryos. Methods Mol Biol 1128:211-21
Kerosuo, Laura; Bronner, Marianne E (2014) Biphasic influence of Miz1 on neural crest development by regulating cell survival and apical adhesion complex formation in the developing neural tube. Mol Biol Cell 25:347-55
Hochgreb-Hägele, Tatiana; Koo, Daniel E S; Das, Neha M et al. (2014) Zebrafish stem/progenitor factor msi2b exhibits two phases of activity mediated by different splice variants. Stem Cells 32:558-71
Cheng, Xianrui; Lyons, Deirdre C; Socolar, Joshua E S et al. (2014) Delayed transition to new cell fates during cellular reprogramming. Dev Biol 391:147-57
Kwon, Seung-Hae; Park, Ok Kyu; Nie, Shuyi et al. (2014) Bioinformatic analysis of nematode migration-associated genes identifies novel vertebrate neural crest markers. PLoS One 9:e103024
Simões-Costa, Marcos; Tan-Cabugao, Joanne; Antoshechkin, Igor et al. (2014) Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory network. Genome Res 24:281-90
Betancur, Paola; Simões-Costa, Marcos; Sauka-Spengler, Tatjana et al. (2014) Expression and function of transcription factor cMyb during cranial neural crest development. Mech Dev 132:38-43

Showing the most recent 10 out of 118 publications