title: Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.
abstract: Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kennedy
authors.forename: Alla
authors.initials: A
authors.lastname: Grishok
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D002843:Chromatin / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D009474:Neurons / Q000166:cytology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D013045:Species Specificity; D040521:Subcutaneous Tissue / Q000196:embryology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D051858:Forkhead Transcription Factors; D020033:Protein Isoforms; D014157:Transcription Factors; C579560:Zfp-1 protein, C elegans; C108831:daf-16 protein, C elegans
keywords: RDE-4; RNAi; ZFP-1/AF10/MLLT10; cell migration; insulin/IGF-1 signaling