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Information processing at the foxa node of the sea urchin endomesoderm specification network

Ben-Tabou de-Leon, Smadar and Davidson, Eric H. (2010) Information processing at the foxa node of the sea urchin endomesoderm specification network. Proceedings of the National Academy of Sciences of the United States of America, 107 (22). pp. 10103-10108. ISSN 0027-8424. PMCID PMC2890477.

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The foxa regulatory gene is of central importance for endoderm specification across Bilateria, and this gene lies at an essential node of the well-characterized sea urchin endomesoderm gene regulatory network (GRN). Here we experimentally dissect the cis-regulatory system that controls the complex pattern of foxa expression in these embryos. Four separate cis-regulatory modules (CRMs) cooperate to control foxa expression in different spatial domains of the endomesoderm, and at different times. A detailed mutational analysis revealed the inputs to each of these cis-regulatory modules. The complex and dynamic expression of foxa is regulated by a combination of repressors, a permissive switch, and multiple activators. A mathematical kinetic model was applied to study the dynamic response of foxa cis-regulatory modules to transient inputs. This study shed light on the mesoderm–endoderm fate decision and provides a functional explanation, in terms of the genomic regulatory code, for the spatial and temporal expression of a key developmental control gene.

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Additional Information:© 2010 by the National Academy of Sciences. Contributed by Eric H. Davidson, April 20, 2010 (sent for review March 10, 2010). Published online before print May 17, 2010. We thank Isabelle Peter, Jongmin Nam, and Joel Smith for valuable comments on the manuscript. We thank Sharon Kuo for help with constructs preparation. This research was supported by National Institutes of Health Grants GM 61005 and HD 37105. S.B.-T.d.-L was a fellow of the Human Frontier Science Program Organization. Author contributions: S.B.-T.d.-L. and E.H.D. designed research; S.B.-T.d.-L. performed research; S.B.-T.d.-L. and E.H.D. analyzed data; and S.B.-T.d.-L. and E.H.D. wrote the paper.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Subject Keywords:cis-regulatory analysis; gene regulatory networks; mathematical modeling; embryonic development
Issue or Number:22
PubMed Central ID:PMC2890477
Record Number:CaltechAUTHORS:20100625-090025829
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:18811
Deposited By: Tony Diaz
Deposited On:03 Aug 2010 21:27
Last Modified:03 Oct 2019 01:48

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