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A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres

Revilla-i-Domingo, Roger and Oliveri, Paola and Davidson, Eric H. (2007) A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres. Proceedings of the National Academy of Sciences of the United States of America, 104 (30). pp. 12383-12388. ISSN 0027-8424. PMCID PMC1941478.

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Specification of sea urchin embryo micromeres occurs early in cleavage, with the establishment of a well defined regulatory state. The architecture of the gene regulatory network controlling the specification process indicates that transcription of the initial tier of control genes depends on a double-negative gate. A gene encoding a transcriptional repressor, pmar1, is activated specifically in micromeres, where it represses transcription of a second repressor that is otherwise active globally. Thus, the micromere-specific control genes, which are the target of the second repressor, are expressed exclusively in this lineage. The double-negative specification gate was logically required from the results of numerous prior experiments, but the identity of the gene encoding the second repressor remained elusive. Here we show that hesC is this gene, and we demonstrate experimentally all of its predicted functions, including global repression of micromere-specific regulatory genes. As logically required, blockade of hesC mRNA translation and global overexpression of pmar1 mRNA have the same effect, which is to cause all of the cells of the embryo to express micromere-specific genes.

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Additional Information:© 2007 by the National Academy of Sciences. Contributed by Eric H. Davidson, June 6, 2007 (received for review April 19, 2007). Published online before print July 16, 2007, 10.1073/pnas.0705324104. We thank Jina Yun for her enormous help in the pmar1 screen; Mary Wahl for carrying out the experiment in SI Table 2; Dr. Qiang Tu for help in alignments and phylogenetic analyses; Dr. Joel Smith for helpful comments on the manuscript; Dr. Jim Coffman for providing an HesC cDNA clone; Pat Leahy for taking care of the sea urchins used for this work; and Sagar Damle for his extremely useful instruction in performing WMISHs and double-WMISHs. This work was supported by National Institutes of Health Grant HD-37105 (to E.H.D.). The authors declare no conflict of interest. This article contains supporting information online at
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Subject Keywords:skeletogenic micromeres; transcriptional repression
Issue or Number:30
PubMed Central ID:PMC1941478
Record Number:CaltechAUTHORS:REVpnas07
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9539
Deposited By: Tony Diaz
Deposited On:31 Jan 2008
Last Modified:03 Oct 2019 00:01

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