(5bz) Intercellular Coupling of Conserved Biomolecular Networks Amplifies Cell Fate Segregation during Development

Completion of several genome projects has produced a wealth of information about the genes that make up the organisms investigated. This knowledge now needs to be enhanced with information on how individual genes work together to produce higher order biological phenomena. Interactions between gene products are most prevalent during development of multicellular organisms when cells send chemical cues to neighboring cells to induce or guide fate patterning. Correct cell fate specification is required for development of functional organs.

Vulva development in the nematode C. elegans is a well known example of robust cell fate specification. Fate patterning of a field of vulval precursor cells occurs when the LIN-3 morphogen is released from a localized source to form a gradient across this field. Cell-cell interactions mediated by LIN-12/Notch receptor and induced by LIN-3 signaling also contribute to pattern specification. In turn, such intercellular lateral interactions lead to expression of negative regulators which diminish the extent of LIN-3 signaling.

Using mathematical modeling this work sought to provide insight into the quantitative implications of the structure of network of interactions between the two fate specifying signaling pathways, LIN-3 and LIN-12. Using a mass action kinetic model we show that coupling LIN-3 and LIN-12 signaling pathways amplifies the cellular perception of LIN-3 gradient and polarizes lateral signaling, both of which enhance cell fate segregation beyond that achieved by an uncoupled system.