It is proposed to construct a computational model which precisely describes the genomic regulatory apparatus required for endomesoderm specification in sea urchin embryos. The model is to be couched in terms of specific, experimentally verifiable or falsifiable predictions that define necessary inputs and outputs of key cis regulatory elements. These are elements which control expression in time and space of genes encoding transcription factors and certain signaling components, which other evidence has identified as relevant genes required in the process of endomesoderm specification. A first stage model of this kind has been built. The investigators will carry out kinetic measurements required to ascertain logical interrelations within the relevant cis regulatory systems and other experiments designed to test architectural features of the computational model. These studies will examine the predicted effects of target site mutations on spatial expression of genes involved in endomesoderm specification, under specific conditions of perturbation. They will also generate a 3D digital construction of the embryo through time, using confocal imaging data, and impose on it the gene expression profiles predicted by the computational regulatory model. The model will ultimately constitute a quantitative computational analysis of a genomic regulatory network, defined at the DNA sequence level, the function of which is to organize a complex, major process in animal development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061005-02
Application #
6387112
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Greenberg, Judith H
Project Start
2000-04-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$271,480
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Longabaugh, William J R (2012) BioTapestry: a tool to visualize the dynamic properties of gene regulatory networks. Methods Mol Biol 786:359-94
Damle, Sagar S; Davidson, Eric H (2012) Synthetic in vivo validation of gene network circuitry. Proc Natl Acad Sci U S A 109:1548-53
Longabaugh, William J R (2012) Combing the hairball with BioFabric: a new approach for visualization of large networks. BMC Bioinformatics 13:275
Peter, Isabelle S; Faure, Emmanuel; Davidson, Eric H (2012) Predictive computation of genomic logic processing functions in embryonic development. Proc Natl Acad Sci U S A 109:16434-42
de-Leon, Smadar Ben-Tabou (2011) The conserved role and divergent regulation of foxa, a pan-eumetazoan developmental regulatory gene. Dev Biol 357:21-6
Ben-Tabou de-Leon, Smadar (2010) Perturbation analysis analyzed--athematical modeling of intact and perturbed gene regulatory circuits for animal development. Dev Biol 344:1110-8
de-Leon, Smadar Ben-Tabou; Davidson, Eric H (2010) Information processing at the foxa node of the sea urchin endomesoderm specification network. Proc Natl Acad Sci U S A 107:10103-8
Davidson, Eric H (2010) Emerging properties of animal gene regulatory networks. Nature 468:911-20
Bolouri, Hamid; Davidson, Eric H (2010) The gene regulatory network basis of the ""community effect,"" and analysis of a sea urchin embryo example. Dev Biol 340:170-8
Nam, Jongmin; Dong, Ping; Tarpine, Ryan et al. (2010) Functional cis-regulatory genomics for systems biology. Proc Natl Acad Sci U S A 107:3930-5

Showing the most recent 10 out of 40 publications