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From the Cover: Feature Article
FEATURE ARTICLE / BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
Global regulatory logic for specification of an embryonic cell lineage
Division of Biology, California Institute of Technology, Pasadena, CA 91125
Edited by Gertrud M. Schüpbach, Princeton University, Princeton, NJ, and approved January 31, 2008 (received for review December 14, 2007)
Explanation of a process of development must ultimately be couched in the terms of the genomic regulatory code. Specification of an embryonic cell lineage is driven by a network of interactions among genes encoding transcription factors. Here, we present the gene regulatory network (GRN) that directs the specification of the skeletogenic micromere lineage of the sea urchin embryo. The GRN now includes all regulatory genes expressed in this lineage up to late blastula stage, as identified in a genomewide survey. The architecture of the GRN was established by a large-scale perturbation analysis in which the expression of each gene in the GRN was cut off by use of morpholinos, and the effects on all other genes were measured quantitatively. Several cis-regulatory analyses provided additional evidence. The explanatory power of the GRN suffices to provide a causal explanation for all observable developmental functions of the micromere lineage during the specification period. These functions are: (i) initial acquisition of identity through transcriptional interpretation of localized maternal cues; (ii) activation of specific regulatory genes by use of a double negative gate; (iii) dynamic stabilization of the regulatory state by activation of a feedback subcircuit; (iv) exclusion of alternative regulatory states; (v) presentation of a signal required by the micromeres themselves and of two different signals required for development of adjacent endomesodermal lineages; and (vi) lineage-specific activation of batteries of skeletogenic genes. The GRN precisely predicts gene expression responses and provides a coherent explanation of the biology of specification.
gene regulatory networks | network subcircuits | sea urchin embryo | skeletogenic micromeres
*Present address: Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom.
This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
See Commentary on page 5951.
This article contains supporting information online at www.pnas.org/cgi/content/full/0711220105/DCSupplemental.
To whom correspondence may be addressed. E-mail: p.oliveri{at}ucl.ac.uk or davidson{at}caltech.edu
© 2008 by The National Academy of Sciences of the USA
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