Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis

Abstract

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.