Dataset Information

Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-? and Dpr10.

ABSTRACT: For animals to perform coordinated movements requires the precise organization of neural circuits controlling motor function. Motor neurons (MNs), key components of these circuits, project their axons from the central nervous system and form precise terminal branching patterns at specific muscles. Focusing on the Drosophila leg neuromuscular system, we show that the stereotyped terminal branching of a subset of MNs is mediated by interacting transmembrane Ig superfamily proteins DIP-? and Dpr10, present in MNs and target muscles, respectively. The DIP-?/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging suggests that precise terminal branching patterns are gradually established by DIP-?/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP-? and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets.

SUBMITTER: Venkatasubramanian L

PROVIDER: S-EPMC6391070 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-α and Dpr10.

Venkatasubramanian Lalanti L Guo Zhenhao Z Xu Shuwa S Tan Liming L Xiao Qi Q Nagarkar-Jaiswal Sonal S Mann Richard S RS

eLife 20190204

For animals to perform coordinated movements requires the precise organization of neural circuits controlling motor function. Motor neurons (MNs), key components of these circuits, project their axons from the central nervous system and form precise terminal branching patterns at specific muscles. Focusing on the <i>Drosophila</i> leg neuromuscular system, we show that the stereotyped terminal branching of a subset of MNs is mediated by interacting transmembrane Ig superfamily proteins DIP-α and ...[more]

PMID: 30714901

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Project description:BackgroundThe characteristic structure of motor neurons (MNs), particularly of the long axons, becomes damaged in the early stages of amyotrophic lateral sclerosis (ALS). However, the molecular pathophysiology of axonal degeneration remains to be fully elucidated.MethodTwo sets of isogenic human-induced pluripotent stem cell (hiPSCs)-derived MNs possessing the single amino acid difference (p.H517D) in the fused in sarcoma (FUS) were constructed. By combining MN reporter lentivirus, MN specific phenotype was analyzed. Moreover, RNA profiling of isolated axons were conducted by applying the microfluidic devices that enable axon bundles to be produced for omics analysis. The relationship between the target gene, which was identified as a pathological candidate in ALS with RNA-sequencing, and the MN phenotype was confirmed by intervention with si-RNA or overexpression to hiPSCs-derived MNs and even in vivo. The commonality was further confirmed with other ALS-causative mutant hiPSCs-derived MNs and human pathology.FindingsWe identified aberrant increasing of axon branchings in FUS-mutant hiPSCs-derived MN axons compared with isogenic controls as a novel phenotype. We identified increased level of Fos-B mRNA, the binding target of FUS, in FUS-mutant MNs. While Fos-B reduction using si-RNA or an inhibitor ameliorated the observed aberrant axon branching, Fos-B overexpression resulted in aberrant axon branching even in vivo. The commonality of those phenotypes was further confirmed with other ALS causative mutation than FUS.InterpretationAnalyzing the axonal fraction of hiPSC-derived MNs using microfluidic devices revealed that Fos-B is a key regulator of FUS-mutant axon branching. FUND: Japan Agency for Medical Research and development; Japanese Ministry of Education, Culture, Sports, Science and Technology Clinical Research, Innovation and Education Center, Tohoku University Hospital; Japan Intractable Diseases (Nanbyo) Research Foundation; the Kanae Foundation for the Promotion of Medical Science; and "Inochi-no-Iro" ALS research grant.

Dataset Information

Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-? and Dpr10.

Publications

Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-α and Dpr10.

Similar Datasets

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