RRC ID 46318
Author Poole RJ, Bashllari E, Cochella L, Flowers EB, Hobert O.
Title A Genome-Wide RNAi Screen for Factors Involved in Neuronal Specification in Caenorhabditis elegans.
Journal PLoS Genet
Abstract One of the central goals of developmental neurobiology is to describe and understand the multi-tiered molecular events that control the progression of a fertilized egg to a terminally differentiated neuron. In the nematode Caenorhabditis elegans, the progression from egg to terminally differentiated neuron has been visually traced by lineage analysis. For example, the two gustatory neurons ASEL and ASER, a bilaterally symmetric neuron pair that is functionally lateralized, are generated from a fertilized egg through an invariant sequence of 11 cellular cleavages that occur stereotypically along specific cleavage planes. Molecular events that occur along this developmental pathway are only superficially understood. We take here an unbiased, genome-wide approach to identify genes that may act at any stage to ensure the correct differentiation of ASEL. Screening a genome-wide RNAi library that knocks-down 18,179 genes (94% of the genome), we identified 245 genes that affect the development of the ASEL neuron, such that the neuron is either not generated, its fate is converted to that of another cell, or cells from other lineage branches now adopt ASEL fate. We analyze in detail two factors that we identify from this screen: (1) the proneural gene hlh-14, which we find to be bilaterally expressed in the ASEL/R lineages despite their asymmetric lineage origins and which we find is required to generate neurons from several lineage branches including the ASE neurons, and (2) the COMPASS histone methyltransferase complex, which we find to be a critical embryonic inducer of ASEL/R asymmetry, acting upstream of the previously identified miRNA lsy-6. Our study represents the first comprehensive, genome-wide analysis of a single neuronal cell fate decision. The results of this analysis provide a starting point for future studies that will eventually lead to a more complete understanding of how individual neuronal cell types are generated from a single-cell embryo.
Volume 7(6)
Pages e1002109
Published 2011-6-1
DOI 10.1371/journal.pgen.1002109
PMID 21698137
PMC PMC3116913
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Lineage / genetics Gene Expression Profiling Gene Expression Regulation, Developmental Genome-Wide Association Study / methods* High-Throughput Screening Assays* Histone Methyltransferases Histone-Lysine N-Methyltransferase / metabolism MicroRNAs / genetics Mutation / genetics Neurons / cytology Neurons / metabolism Neurons / pathology RNA Interference* Reproducibility of Results
IF 5.175
Times Cited 22
C.elegans tm295 tm3463 tm3530 tm1956 tm1905 tm645