An Epidermal MicroRNA Regulates Neuronal Migration Through Control of the Cellular Glycosylation State

Pedersen, M. E.; Snieckute, Goda; Kagias, Konstantinos; Nehammer, Camilla; Multhaupt, Hinke A.B.; Couchman, John R.; Pocock, Roger

doi:10.1126/science.1242528

Cited by 79 publications

(68 citation statements)

References 39 publications

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“…Consistently, we also find that the cDNA of the long isoform of zfp-1 fused to GFP driven by the unc-86 promoter, which is expressed in a subset of neurons including the HSN (Baumeister et al 1996), does not rescue the HSN undermigration defects seen in zfp-1(ok554) mutants ( Figure S2, A and B). Interestingly, a conserved microRNA has also been recently reported to function nonautonomously in the hypodermis to regulate genes required for proteoglycan biosynthesis to ensure proper HSN migration (Pedersen et al 2013). Overall, the action of ZFP-1 in controlling DAF-16 dynamics in the hypodermis that we describe here complements well our earlier findings of the nonautonomous roles of both DAF-16 and DAF-18 (PTEN) in regulating HSN migration ( Figure 2B) (Kennedy et al 2013).…”

Section: Zfp-1(ok554) Limits Daf-16 Nuclear Localization In the Embrysupporting

confidence: 78%

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

Kennedy

Grishok

2014

Genetics

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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 hermaphroditespecific 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.

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Section: Zfp-1(ok554) Limits Daf-16 Nuclear Localization In the Embrysupporting

confidence: 78%

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

Kennedy

Grishok

2014

Genetics

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“…Indeed, ectopic expression of lin-29 in the intestine rescues the vitellogenesis defects in the lin-29 mutant, suggesting that LIN-29 may directly activate expression of a soluble intertissue signaling molecule that is perceived by intestinal cells. Interestingly, proper migration of the hermaphrodite-specific neurons and arborization of the sensory dendrites during development are mediated by hypodermal expressed cell surface receptors or adhesion molecules, further underscoring the role of the hypodermis in non-cell-autonomous developmental regulation (Pedersen et al 2013;Salzberg et al 2013).…”

Section: Discussionmentioning

confidence: 99%

A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport

et al. 2016

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Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell-autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline.

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“…In C. elegans, the miR-9 homolog miR-79 was shown to interfere with proteoglycan synthesis and thereby prevent hermaphroditespecific neuron (HSN) migration (Pedersen et al, 2013). In mice, global miRNA reduction (via Nestin-Cre-mediated Dicer1 deletion) in late-born embryonic neurons impairs the migration of neurons into upper cortical layers (Kawase-Koga et al, 2009).…”

Section: Migrationmentioning

confidence: 99%

MicroRNAs in neural development: from master regulators to fine-tuners

2017

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The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. It is wellestablished that transcriptional programs play major roles in neural circuit development. However, in recent years, post-transcriptional control of gene expression has emerged as an additional, and probably equally important, regulatory layer. In particular, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation. It is also becoming clear that miRNAs are frequently dysregulated in neurodevelopmental disorders, suggesting a role for miRNAs in the etiology and/or maintenance of neurological disease states. Here, we provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as 'master regulators' or 'fine-tuners' of gene expression, depending on context, to influence processes such as cell fate determination, cell migration, neuronal polarization and synapse formation.

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An Epidermal MicroRNA Regulates Neuronal Migration Through Control of the Cellular Glycosylation State

Cited by 79 publications

References 39 publications

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport

MicroRNAs in neural development: from master regulators to fine-tuners

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