Conserved RNA-binding proteins required for dendrite morphogenesis in Caenorhabditis elegans sensory neurons.
Bottom Line: Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons.Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species.Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans.
Affiliation: Department of Molecular Biology, Colorado College, Colorado Springs, Colorado 80903.Show MeSH
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Mentions: We found that the loss or reduction of function of 12 RBP genes, individually, resulted in a statistically significant reduction in PVD dendritic termini compared with control animals (Table 1, Figure 1, and Figure 2A). Whereas control animals at the young adult stage have an average of 23 dendritic termini in the region scored, mutations in cgh-1, cpb-3, dcr-1, larp-5, mbl-1, mtr-4, rsp-3, rsp-6, set-2, and sup-26 all result in at least a 20% reduction in dendrite termini (Figure 1B and Figure 2A). Although RNAi screening was less effective at identifying RBP genes important for dendrite morphogenesis (see the section Discussion), we did find that ddx-17 and Y55F3AM.3 RNAi-treated animals showed a 14% and 11% respective reduction in the number of dendritic termini compared to untreated control animals (Figure 1C and Figure 2A). After completing the RNAi screen, we tested several point mutations in Y55F3AM.3 generated by the Million Mutation Project (Thompson et al. 2013) to identify a reduction-of-function allele. One allele, gk454899, affects a conserved residue across Drosophila, zebrafish, and mammals and resulted in a 19% reduction of dendritic termini compared to control animals (Table S1, Figure 1B, and Figure 2A).
Affiliation: Department of Molecular Biology, Colorado College, Colorado Springs, Colorado 80903.