Research

Experimental solution of gene regulatory networks

In the past we solved the regulatory circuits specifying endodermal progenitors up to the onset of gastrulation (30h) which provides a promising start for the discovery of genomic programs underlying gut organogenesis. Sea urchin larvae form a complete gut consisting of foregut, stomach, hindgut, cardiac sphincter, pyloric sphincter, mouth and anus within 72h after fertilization.  To study the GRN underlying gut organogenesis, we are performing systematic perturbations of transcription factors expressed in cell fate-specific regulatory states and analyze the consequence of these perturbations on all other regulatory genes in the system. We then use these data to construct topological GRN models that display the architecture of newly discovered regulatory circuits.

Cui, Miao and Vielmas, Erika and Davidson, Eric H. and Peter, Isabelle S. (2017) Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis- Regulatory Module of Sea Urchin hox11/13b. Cell Reports, 19 (2), 364-374.pdf

Peter, Isabelle S. and Davidson, Eric H. (2011) A gene regulatory network controlling the embryonic specification of endoderm. Nature, 474 (7353), 635-639.pdf

Peter, Isabelle S. and Davidson, Eric H. (2010) The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage. Developmental Biology, 340 (2), 188-199.pdf

Cui, Miao and Siriwon, Natnaree and Li, Enhu and Davidson, Eric H. and Peter, Isabelle S. (2014) Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo. Proceedings of the National Academy of Sciences of the United States of America, 111 (47). E5029-E5038.pdf

 

Analysis of combinatorial regulatory states

The spatial organization of an organism is established during development by expression of combinations of transcription factors, or regulatory states. To learn about the information contained in regulatory states, we are experimentally analyzing the regulatory states that are expressed throughout the sea urchin embryo during the first three days of development. By comparing regulatory states expressed in different spatial domains and at different developmental times, we gain insights into how developmental changes in the control of gene expression establish the spatial organization of the sea urchin larva.

 

Computational models of gene regulatory networks

The sea urchin endomesoderm GRN model contains about 50 regulatory genes. Based on the regulatory interactions included in this model, we generated a Boolean model to compute the spatial and temporal expression of all genes in this network. This Boolean model demonstrates that the endomesoderm GRN is sufficient to account for the cell-fate specific regulatory states established during early sea urchin development. We are now applying this computational approach to test the behavior of regulatory circuits, and we perform in silico perturbations to reveal circuit design features that are crucial for biological function.

Peter, Isabelle S. and Davidson, Eric H. (2017) Assessing regulatory information in developmental gene regulatory networks. Proceedings of the National Academy of Sciences of the United States of America, 114 (23), 5862-5869.pdf

Peter, Isabelle S. and Faure, Emmanuel and Davidson, Eric H. (2012) Predictive computation of genomic logic processing functions in embryonic development. Proceedings of the National Academy of Sciences of the United States of America, 109 (41), 16434-16442.pdf

Faure, Emmanuel and Peter, Isabelle S. and Davidson, Eric H. (2013) A New Software Package for Predictive Gene Regulatory Network Modeling and Redesign. Journal of Computational Biology, 20 (6), 419-423.pdf

Evolution of developmental processes

 Evolution of the body plan is the result of changes in the architecture of GRNs. The particular hierarchical organization of developmental GRNs, and the modular subcircuits they consist of, have implications also on how GRNs evolve and on the biological consequences of regulatory changes within GRNs. Using a theoretical approach, we aim at predicting how mutations at different positions within GRN architecture might affect evolutionary outcome. However, we also use experimental approaches to explore how changes in GRN architecture have affected the function of the endomesoderm GRN within echinoderms.

Concepts of genomic control systems

Solving the regulatory circuits encoded in animal genomes is time consuming, particularly in more complex organisms. But where GRNs have been solved, they explain how body plans are organized, how cell fates are established, how signals are interpreted in context-specific ways, how developmental timing is controlled, and many other aspects of developmental processes. By evaluating the design of known regulatory circuits that control these biological functions, we are trying to establish a connection between GRN architecture and GRN function. Using experiences from organisms with simpler body plans we aim at developing concepts for regulatory circuits that will facilitate the analysis and interpretation of genomic programs in more complex organisms.

Peter, Isabelle S. and Davidson, Eric H. (2017) Assessing regulatory information in developmental gene regulatory networks. Proceedings of the National Academy of Sciences of the United States of America, 114 (23), 5862-5869.pdf

Peter, Isabelle S. (2017) Regulatory states in the developmental control of gene expression. Briefings in Functional Genomics. 16(5), 281-287 .pdf

Peter, Isabelle S. and Davidson, Eric H. (2016) Implications of Developmental Gene Regulatory Networks Inside and Outside Developmental Biology. In: Essays on Developmental Biology. Current Topics in Developmental Biology. Vol.B. No.117. Academic Press , Cambridge, Mass., pp. 237-251.

Peter, Isabelle S. and Davidson, Eric H. (2015) Genomic Control Process. Development and Evolution Academic Press , San Diego.