The broad goal of this work is to understand the genetic and molecular mechanisms of temporal control of cell division and differentiation using the nematode C. elegans as a model. Genetic and molecular analysis will be performed to determine how the regulatory pathway of heterochronic genes controls the temporally coordinated expression of diverse developmental events in C. elegans larvae. Emphasis will be placed on understanding how certain genes control the timing of events in diverse cell types, and how other genes act to specify the execution of particular events. Genetic screens will be employed to identify new genes in this pathway. Key genes will be analysed molecularly to determine the structure and expression of their products, and how they interact with the products of other heterochronic genes. Mosaic analysis will be used to assess the role of these genes in cell-cell signalling processes that coordinate developmental programs in separate cell lineages. Emphasis will be placed on understanding the molecular mechanism of how lin-14, a gene that plays a central role in the control of diverse larval cell lineages, is regulated by the novel regulatory molecule encoded by lin-4. Also a major effort will be focused on understanding how the transcription factor encoded by lin-29 is developmentally regulated, and how it controls the transcription of adult-specific and larval-specific genes. Generally speaking, the C. elegans heterochronic genes offer an opportunity to study the genetic and molecular mechanisms controlling cell division and differentiation, processes central to all multicellular development. More specifically, the fact that the heterochronic genes affect developmental timing provides a unique system in which to examine in detail the regulatory mechanisms underlying temporal control.
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