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Comments on Bashllari, Enkelejda et al. (2009) International Worm Meeting "Genome-wide RNAi analysis of neuronal cell fate and left/right asymmetry in C. elegans." (0)
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Bashllari, Enkelejda, Poole, Richard, & Hobert, Oliver (2009). Genome-wide RNAi analysis of neuronal cell fate and left/right asymmetry in C. elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
The developmental programs that lead to the specification of individual neuron types in a nervous system remain incompletely understood. Forward and reverse genetic screens have served as a valuable tool to identify genes involved in neuronal fate specification. We describe here the results of a genome-wide RNAi screen to uncover factors involved in the specification of a single neuronal sub-type in the nematode C. elegans. In wild-type animals, the two morphologically bilaterally symmetric gustatory neurons ASE left (ASEL) and ASE right (ASER) undergo a left/right asymmetric diversification in cell fate, manifested by the differential expression of a class of putative chemoreceptors and neuropeptides. Using an asymmetrically expressed ASEL-specific GFP reporter we have screened ~14,000 RNAi targeted genes for novel factors that play a role in the development, specification and maintenance of ASE neuronal identity. Thus far, we have identified 254 genes whose knockdown by RNAi produces a loss of the ASEL fate or a gain of an ectopic ASEL; only 5 of these were previously known to affect ASE development. Further analysis of the uncovered genes places them in several distinctive phenotypic categories; genes that affect early blastomere identity (par-3, mex-5, etc) whose division defects produce lineage transformations expected to create ectopic ASEs, overall neuronal cell fate specification factors such as the transcription factor achaete-scute/hlh-14 (see abstract by Poole, Bashllari and Hobert) and classical asymmetry genes such as F27D4.2 which specify neuronal sub-type by left/right asymmetry within a neuron class. Their molecular identity places these genes in several categories with the ones of most interest to us being proteins involved in signaling, RNA-binding, transcription and chromatin regulation. The subsequent detailed characterization of the identified genes in the aforementioned categories is expected to provide more insight into the complex genetic architecture of neuronal cell fate specification and sub-type left/right asymmetric decision.