Atsushi Ueda, Tristan C D G O'Harrow, Xiaomin Xing, Salleh Ehaideb, J Robert Manak, Chun-Fang Wu
{"title":"棘果蝇异型突变体的异常幼体神经肌肉连接形态和生理,已知轴突运输缺陷和成年癫痫行为。","authors":"Atsushi Ueda, Tristan C D G O'Harrow, Xiaomin Xing, Salleh Ehaideb, J Robert Manak, Chun-Fang Wu","doi":"10.1080/01677063.2022.2093353","DOIUrl":null,"url":null,"abstract":"<p><p>Previous studies have demonstrated the striking mutational effects of the <i>Drosophila</i> planar cell polarity gene <i>prickle (pk)</i> on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the <i>prickle</i>-<i>prickle</i> (<i>pk<sup>pk</sup></i>) and <i>prickle</i>-<i>spiny-legs</i> (<i>pk<sup>sple</sup></i>) isoforms (hereafter referred to as <i>pk</i> and <i>sple</i> alleles, respectively) exhibit differential phenotypes. While both <i>pk</i> and <i>sple</i> affect larval motor axon transport, only <i>sple</i> confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic <i>pk<sup>pk</sup>/pk<sup>spl</sup></i><sup>e</sup> flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both <i>pk</i> and <i>sple</i> alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in <i>pk/pk</i> larvae, i.e. increased excitatory junctional potential (EJP) amplitude in <i>pk/pk</i> but not in <i>pk</i>/+ or <i>sple</i>/<i>sple</i>. Interestingly, for motor terminal excitability sustained by presynaptic Ca<sup>2+</sup> channels, both <i>pk</i> and <i>sple</i> exerted strong effects to produce prolonged depolarization. Notably, only <i>sple</i> acted dominantly whereas <i>pk</i>/+ appeared normal, but was able to suppress the <i>sple</i> phenotypes, i.e. <i>pk/sple</i> appeared normal. Our observations contrast the differential roles of the <i>pk</i> and <i>sple</i> isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Abnormal larval neuromuscular junction morphology and physiology in <i>Drosophila</i> prickle isoform mutants with known axonal transport defects and adult seizure behavior.\",\"authors\":\"Atsushi Ueda, Tristan C D G O'Harrow, Xiaomin Xing, Salleh Ehaideb, J Robert Manak, Chun-Fang Wu\",\"doi\":\"10.1080/01677063.2022.2093353\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Previous studies have demonstrated the striking mutational effects of the <i>Drosophila</i> planar cell polarity gene <i>prickle (pk)</i> on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the <i>prickle</i>-<i>prickle</i> (<i>pk<sup>pk</sup></i>) and <i>prickle</i>-<i>spiny-legs</i> (<i>pk<sup>sple</sup></i>) isoforms (hereafter referred to as <i>pk</i> and <i>sple</i> alleles, respectively) exhibit differential phenotypes. While both <i>pk</i> and <i>sple</i> affect larval motor axon transport, only <i>sple</i> confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic <i>pk<sup>pk</sup>/pk<sup>spl</sup></i><sup>e</sup> flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both <i>pk</i> and <i>sple</i> alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in <i>pk/pk</i> larvae, i.e. increased excitatory junctional potential (EJP) amplitude in <i>pk/pk</i> but not in <i>pk</i>/+ or <i>sple</i>/<i>sple</i>. Interestingly, for motor terminal excitability sustained by presynaptic Ca<sup>2+</sup> channels, both <i>pk</i> and <i>sple</i> exerted strong effects to produce prolonged depolarization. Notably, only <i>sple</i> acted dominantly whereas <i>pk</i>/+ appeared normal, but was able to suppress the <i>sple</i> phenotypes, i.e. <i>pk/sple</i> appeared normal. Our observations contrast the differential roles of the <i>pk</i> and <i>sple</i> isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.</p>\",\"PeriodicalId\":16491,\"journal\":{\"name\":\"Journal of neurogenetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neurogenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/01677063.2022.2093353\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurogenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01677063.2022.2093353","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior.
Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.
期刊介绍:
The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms