Drosophila Shep and C. elegans SUP-26 are RNA-binding proteins that play diverse roles in nervous system development

Schachtner, Logan T.; Sola, Ismail; Forand, Daniel; Antonacci, Simona; Postovit, Adam J.; Mortimer, Nathan T.; Killian, Darrell J.; Olesnicky, Eugenia C.

doi:10.1007/s00427-015-0514-3

Cited by 10 publications

(9 citation statements)

References 57 publications

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“…Additionally, disruption of either shep or cut function is associated with shortened dendritic branches and field coverage defects. Moreover, cut and shep mutant phenotypes are also highly variable and not fully penetrant, similar to those observed for various caper CC01391 mutant neuronal phenotypes (Schachtner et al, ; Grueber et al, ). In addition to these regulators of branch length, caper CC01391 mutant embryos show aberrant alternative isoform regulation for the gene fry .…”

Section: Discussionsupporting

confidence: 73%

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: Discussionsupporting

confidence: 73%

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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“…The alan shepard ( shep ) gene is widely and primarily expressed in the nervous system and has been shown to regulate metamorphic neuronal outgrowth and development (Chen et al 2014; Schachtner et al 2015). Loss of shep leads to defective outgrowth of peptidergic bursicon neurons, developmental lethality, and behavioral defects, all of which are largely adult-specific (Chen et al 2014).…”

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confidence: 99%

“…Loss of shep leads to defective outgrowth of peptidergic bursicon neurons, developmental lethality, and behavioral defects, all of which are largely adult-specific (Chen et al 2014). Loss of shep also interferes with the development of nociceptive and proprioceptive neurons in the larval peripheral nervous system (Schachtner et al 2015). In addition, the shep gene has been identified in a number of screens for factors involved in gravitaxis (Armstrong et al 2006), regulation of fat storage (Reis et al 2010), starvation resistance (Harbison et al 2004), cell size determination (Bjorklund et al 2006), and mRNA alternative splicing (Brooks et al 2015).…”

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confidence: 99%

Regulatory Mechanisms of Metamorphic Neuronal Remodeling Revealed Through a Genome-Wide Modifier Screen in Drosophila melanogaster

Chen

Pham

et al. 2017

Genetics

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During development, neuronal remodeling shapes neuronal connections to establish fully mature and functional nervous systems. Our previous studies have shown that the RNA-binding factor alan shepard (shep) is an important regulator of neuronal remodeling during metamorphosis in Drosophila melanogaster, and loss of shep leads to smaller soma size and fewer neurites in a stage-dependent manner. To shed light on the mechanisms by which shep regulates neuronal remodeling, we conducted a genetic modifier screen for suppressors of shep-dependent wing expansion defects and cellular morphological defects in a set of peptidergic neurons, the bursicon neurons, that promote posteclosion wing expansion. Out of 702 screened deficiencies that covered 86% of euchromatic genes, we isolated 24 deficiencies as candidate suppressors, and 12 of them at least partially suppressed morphological defects in shep mutant bursicon neurons. With RNA interference and mutant alleles of individual genes, we identified Daughters against dpp (Dad) and Olig family (Oli) as shep suppressor genes, and both of them restored the adult cellular morphology of shep-depleted bursicon neurons. Dad encodes an inhibitory Smad protein that inhibits bone morphogenetic protein (BMP) signaling, raising the possibility that shep interacted with BMP signaling through antagonism of Dad. By manipulating expression of the BMP receptor tkv, we found that activated BMP signaling was sufficient to rescue loss-of-shep phenotypes. These findings reveal mechanisms of shep regulation during neuronal development, and they highlight a novel genetic shep interaction with the BMP signaling pathway that controls morphogenesis in mature, terminally differentiated neurons during metamorphosis.

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“…A screen for RBPs and translation factors that are specifically required for dendrite development within Class IV da neurons uncovered 88 candidate genes that regulate dendrite morphology in Class IV da neurons [ 92 ]. Subsequent studies have confirmed that a number of these candidate genes, including brat, shep, caper, 4EHP, oskar and rumpelstiltskin, indeed function in da neuron morphogenesis, and that 12 of these RBPs play a conserved role in dendrite development in C. elegans [ 88 , 93 , 94 , 95 ]. The fact that almost all of these candidates are conserved across metazoa suggests that RNA regulatory mechanisms are critical to the development and function of the nervous system.…”

Section: Additional Roles For Rbps Throughout Drosophilamentioning

confidence: 99%

Drosophila as a Model for Assessing the Function of RNA-Binding Proteins during Neurogenesis and Neurological Disease

Olesnicky

Wright

2018

JDB

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An outstanding question in developmental neurobiology is how RNA processing events contribute to the regulation of neurogenesis. RNA processing events are increasingly recognized as playing fundamental roles in regulating multiple developmental events during neurogenesis, from the asymmetric divisions of neural stem cells, to the generation of complex and diverse neurite morphologies. Indeed, both asymmetric cell division and neurite morphogenesis are often achieved by mechanisms that generate asymmetric protein distributions, including post-transcriptional gene regulatory mechanisms such as the transport of translationally silent messenger RNAs (mRNAs) and local translation of mRNAs within neurites. Additionally, defects in RNA splicing have emerged as a common theme in many neurodegenerative disorders, highlighting the importance of RNA processing in maintaining neuronal circuitry. RNA-binding proteins (RBPs) play an integral role in splicing and post-transcriptional gene regulation, and mutations in RBPs have been linked with multiple neurological disorders including autism, dementia, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Fragile X syndrome (FXS), and X-linked intellectual disability disorder. Despite their widespread nature and roles in neurological disease, the molecular mechanisms and networks of regulated target RNAs have been defined for only a small number of specific RBPs. This review aims to highlight recent studies in Drosophila that have advanced our knowledge of how RBP dysfunction contributes to neurological disease.

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Drosophila Shep and C. elegans SUP-26 are RNA-binding proteins that play diverse roles in nervous system development

Cited by 10 publications

References 57 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

Regulatory Mechanisms of Metamorphic Neuronal Remodeling Revealed Through a Genome-Wide Modifier Screen in Drosophila melanogaster

Drosophila as a Model for Assessing the Function of RNA-Binding Proteins during Neurogenesis and Neurological Disease

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