Nature 436, 861-865 (11 August 2005) | doi:10.1038/nature03876; Received 30 March 2005; Accepted 23 May 2005

Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis

Kristin C. Gunsalus1,6, Hui Ge2,6, Aaron J. Schetter1,6, Debra S. Goldberg3,6, Jing-Dong J. Han2, Tong Hao2, Gabriel F. Berriz3, Nicolas Bertin2, Jerry Huang1, Ling-Shiang Chuang1, Ning Li2, Ramamurthy Mani3, Anthony A. Hyman4, Birte Sönnichsen5, Christophe J. Echeverri5, Frederick P. Roth3, Marc Vidal2 & Fabio Piano1

  1. Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA
  2. Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
  3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Massachusetts 02115, USA
  4. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
  5. Cenix BioScience GmbH, 01307 Dresden, Germany
  6. *These authors contributed equally to this work

Correspondence to: Frederick P. Roth3Marc Vidal2Fabio Piano1 Correspondence and requests for materials should be addressed to F.P. (Email: fp1@nyu.edu), M.V. (Email: marc_vidal@dfci.harvard.edu) or F.P.R. (Email: fritz_roth@hms.harvard.edu).

Although numerous fundamental aspects of development have been uncovered through the study of individual genes and proteins, system-level models are still missing for most developmental processes. The first two cell divisions of Caenorhabditis elegans embryogenesis constitute an ideal test bed for a system-level approach. Early embryogenesis, including processes such as cell division and establishment of cellular polarity, is readily amenable to large-scale functional analysis. A first step toward a system-level understanding is to provide 'first-draft' models both of the molecular assemblies involved1 and of the functional connections between them. Here we show that such models can be derived from an integrated gene/protein network generated from three different types of functional relationship2: protein interaction3, expression profiling similarity4 and phenotypic profiling similarity5, as estimated from detailed early embryonic RNA interference phenotypes systematically recorded for hundreds of early embryogenesis genes6. The topology of the integrated network suggests that C. elegans early embryogenesis is achieved through coordination of a limited set of molecular machines. We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo.


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