Gene regulatory networks uderlying cell fate specification of a C. elegans sensory/inter/motor neuron-type

Abstract

Neuronal specification and differentiation are orchestrated through external and internal molecules including transcription factors. However, the mechanisms of how specific transcription factors determine or specify neuronal cell fate during development are not fully understood. In C. elegans, the IL1 sensory/inter/motor neurons consist of six neurons that regulate the rate and pattern of spontaneous foraging movement (Kaplan et al., 1997). To identify molecular and cellular mechanisms by which the IL1 neurons are terminally differentiated, we searched for cis-and trans-acting factors that are necessary and sufficient for specification of the IL1 neurons. First, we performed promoter analysis of the set of genes that are specifically expressed in IL1s, including flp-3neuropeptide gene (Kim et al., 2004). We found several cis-regulatory regions of which deletion caused decreased flp-3expression in the IL1 neurons. More specifically, we identified a motif (referred to as the IL1L/R motif) that is necessary for flp-3expression specifically in the IL1L/R neurons. We are currently testing whether this motif exists in promoters of other IL1-expressed genes and this motif is also sufficient for the expression in IL1L/R. In addition, we performed candidate gene searches and mutagenesis screens to identify trans-acting factor of IL1s, and found that several genes including ceh-43or unc-86regulate flp-3expression in the IL1 neurons. We also isolated several mutant animals which show decreased flp-3expression in the IL1 neurons. We are currently identifying molecular lesions in these mutants.