This is the lead Component of the Program Project. Its overall objective is to expand understanding, by direct experimental determination, of the sea urchin embryo gene regulatory network (GRN) so as to encompass specification and differentiation of oral and aboral ectoderm, mesoderm, and endoderm territories up until late gastrula period. This means that with the exception of the apical neurogenic territory (provisionally excepted to avoid redundancy with other labs), and with the exception of a few developmental territorial specifications which occur only late in embryogenesis, the entire embryo will be included in the GRN. This project will yield, for the first time in any example of animal embryonic development, a system-level model of the global genomic regulatory program for the design of the embryo. It will explain the establishment of the spatial regulatory states that define most of its territories, and that ultimately serve to drive differentiation. As shown by current results with the sea urchin embryo endomesodermal GRN (which extends only to the onset of gastrulation) the benefits to scientific knowledge of development that can confidently be expected if the main objective of this proposal can be met, are as follows: (1) The GRN model can and will be validated by direct mutational cis-regulatory analysis at its key nodes and the model is therefore a solid, predictive, and specific, indication of the genomic regulatory system that underlies all embryonic development. (2) The GRN will provide a causal explanation of the biology of embryonic specification, and on a global scale, of the design of the embryo: it will answer why events proceed as they do. (3) The GRN will provide the comparative evidence required to discern the most deeply embedded subcircuits or kernels of mammalian genomic regulatory systems for endoderm, mesoderm, and perhaps ectoderm development. New system level technologies, instrumentation, and enhanced throughput methods of procedure which are already in hand make the ambitious objective of this proposal feasible, and its extensive computational underpinnings are supported by a complementary grant from the NIGMS which has just been renewed. This Component of the Program Project is basic to the success of the other Components: these consist of extensions of the GRN downstream, to encompass the functions of morphogenesis (Component II);its extension into a 4D model of the embryo (Component III);and in addition, transfer of GRN analysis concepts to a vertebrate developmental specification system (Component IV).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD037105-15
Application #
8471137
Study Section
Special Emphasis Panel (ZHD1-DSR-Z)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
15
Fiscal Year
2013
Total Cost
$477,731
Indirect Cost
$98,980
Name
California Institute of Technology
Department
Type
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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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

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