RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches

Mikl, Martin; Vendra, Georgia; Doyle, Michael; Kiebler, Michael

doi:10.1007/s00359-010-0520-x

Cited by 23 publications

(12 citation statements)

References 104 publications

(139 reference statements)

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“…Studies have shown that alternative mRNA isoforms are differentially localized within cells. Indeed, mRNA localization has been shown to be important for the morphogenesis of many cell types, including neurons, and aberrant mRNA localization has been implicated in various neurological diseases (Tolino et al, ; Holt and Schuman, ; Job and Eberwine, ; Doyle and Kiebler, ; Schuman et al, ; Brechbiel and Gavis, ; Mikl et al, ; Vessey et al, ). For example, alternative brain‐derived neurotrophic factor (Bdnf) mRNA isoforms show distinct localization patterns in neurons, where a short isoform is restricted to the cell body and a long isoform is instead localized to the dendritic compartment.…”

Section: Discussionmentioning

confidence: 99%

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

Olesnicky

Bono

Bell

et al. 2017

Developmental Dynamics

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Background Alternative splicing mediated by RNA-binding proteins (RBPs) is emerging as a fundamental mechanism for the regulation of gene expression. Alternative splicing has been shown to be a widespread phenomenon that facilitates the diversification of gene products in a tissue specific manner. Although defects in alternative splicing are rooted in many neurological disorders, only a small fraction of splicing factors have been investigated in detail. Results We find that the splicing factor Caper is required for the development of multiple different mechanosensory neuron subtypes at multiple life stages in Drosophila melanogaster. Disruption of Caper function causes defects in dendrite morphogenesis of larval dendrite arborization neurons, neuronal positioning of embryonic proprioceptors, as well as the development and maintenance of adult mechanosensory bristles. Additionally, we find that Caper dysfunction results in aberrant locomotor behavior in adult flies. Transcriptome-wide analyses further support a role for Caper in alternative isoform regulation of genes that function in neurogenesis. Conclusions Our results provide the first evidence for a fundamental and broad requirement for the highly conserved splicing factor Caper in the development and maintenance of the nervous system and provide a framework for future studies on the detailed mechanism of Caper mediated RNA regulation.

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Section: Discussionmentioning

confidence: 99%

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

Olesnicky

Bono

Bell

et al. 2017

Developmental Dynamics

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“…As described above, results from the secondary RNAi screen indicate that a large number of the identified genes influence dendrite morphogenesis in class IV da neurons. While many studies have investigated requirements for the localization of mRNAs and/or RNA binding proteins and translation factors during the morphogenesis and remodeling of postsynaptic dendritic spines ( Mikl et al 2010 ; Thomas et al 2014 ), the role of mRNA localization and local translation in the gross morphogenesis of dendritic arbors has not been addressed to the same extent. Our previous work utilized the MS2 /MCP system to demonstrate that the localization of nanos mRNA is essential for proper dendritic branch morphogenesis in class IV da neurons ( Brechbiel and Gavis 2008 ).…”

Section: Discussionmentioning

confidence: 99%

A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

Misra

Edmund

Ennis

et al. 2016

G3 Genes|Genomes|Genetics

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Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

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“…Post-transcriptional mechanisms of gene regulation such as translational control play a fundamental role in the development and function of the nervous system (Eberwine et al, 2001; Mikl et al, 2010; Schuman et al, 2006; Job et al, 2001; Martin, 2004). Genetic studies have identified roles for the translational repressors Nos and Pum in sensory neuron and NMJ morphogenesis, NMJ function, and motor neuron excitability, and Pum has been implicated in long-term memory (Baines 2005).…”

Section: Discussionmentioning

confidence: 99%

Combinatorial use of translational co-factors for cell type-specific regulation during neuronal morphogenesis in Drosophila

Olesnicky

Bhogal

Gavis

2012

Developmental Biology

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The translational regulators Nanos (Nos) and Pumilio (Pum) work together to regulate the morphogenesis of dendritic arborization (da) neurons of the Drosophila larval peripheral nervous system. In contrast, Nos and Pum function in opposition to one another in the neuromuscular junction to regulate the morphogenesis and the electrophysiological properties of synaptic boutons. Neither the cellular functions of Nos and Pum nor their regulatory targets in neuronal morphogenesis are known. Here we show that Nos and Pum are required to maintain the dendritic complexity of da neurons during larval growth by promoting the outgrowth of new dendritic branches and the stabilization of existing dendritic branches, in part by regulating the expression of cut and head involution defective. Through an RNA interference screen we uncover a role for the translational co-factor Brain Tumor (Brat) in dendrite morphogenesis of da neurons and demonstrate that Nos, Pum, and Brat interact genetically to regulate dendrite morphogenesis. In the neuromuscular junction, Brat function is most likely specific for Pum in the presynaptic regulation of bouton morphogenesis. Our results reveal how the combinatorial use of co-regulators like Nos, Pum and Brat can diversify their roles in post-transcriptional regulation of gene expression for neuronal morphogenesis.

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RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches

Cited by 23 publications

References 104 publications

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

Combinatorial use of translational co-factors for cell type-specific regulation during neuronal morphogenesis in Drosophila

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