scholarly journals Abnormal larval neuromuscular junction morphology and physiology in Drosophila Prickle isoform mutants with defective axonal transport and adult seizure behavior

2022 ◽  
Author(s):  
Tristan O'Harrow ◽  
Atsushi Ueda ◽  
Xiaomin Xing ◽  
Salleh N Ehaideb ◽  
John R Manak ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Planar Cell Polarity ◽  
Vesicle Release ◽  
Functional Aspects ◽  
Pharmacological Blockade ◽  
Synaptic Boutons ◽  
Channel Dependent ◽  
Larval Neuromuscular Junction ◽  
Terminal Excitability ◽  
Polarity Gene

Previous studies have demonstrated that mutations of the Drosophila planar cell polarity gene prickle (pk) result in altered microtubule-mediated vesicular transport in larval motor axons, as well as adult neuronal circuit hyperexcitability and epileptic behavior. It is also known that mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms differ in phenotype but display isoform counterbalancing effects in heteroallelic pkpk/pksple flies to ameliorate adult motor circuit and behavioral hyperexcitability. We have further investigated the larval neuromuscular junction (NMJ) and uncovered robust phenotypes in both pkpk and pksple alleles (heretofore referred to as pk and sple alleles, respectively), including synaptic terminal overgrowth, as well as irregular motor axon terminal excitability, poor vesicle release synchronicity, and altered efficacy of synaptic transmission. We observed significant increase in whole-cell excitatory junctional potential (EJP) in pk homozygotes, which was restored to near WT level in pk/sple heterozygotes. We further examined motor terminal excitability sustained by presynaptic Ca2+ channels, under the condition of pharmacological blockade of Na+ and K+ channel function. Such manipulation revealed extreme Ca2+ channel-dependent nerve terminal excitability in both pk and sple mutants. However, when combined in pk/sple heterozygotes, such terminal hyper-excitability was restored to nearly normal. Focal recording from individual synaptic boutons revealed asynchronous vesicle release in both pk and sple homozygotes, which nevertheless persisted in pk/sple heterozygotes without indications of isoform counter-balancing effects. Similarly, the overgrowth at NMJs was not compensated in pk/sple heterozygotes, exhibiting an extremity comparable to that in pk and sple homozygotes. Our observations uncovered differential roles of the pk and sple isoforms and their distinct interactions in the various structural and functional aspects of the larval NMJ and adult neural circuits.

scholarly journals Input-Specific Plasticity and Homeostasis at the Drosophila Larval Neuromuscular Junction

Neuron ◽  
2017 ◽  
Vol 93 (6) ◽  
pp. 1388-1404.e10 ◽  
Author(s):  
Zachary L. Newman ◽  
Adam Hoagland ◽  
Krishan Aghi ◽  
Kurtresha Worden ◽  
Sabrina L. Levy ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Larval Neuromuscular Junction

scholarly journals The core planar cell polarity gene, Vangl2 , maintains apical‐basal organisation of the corneal epithelium

2017 ◽  
Vol 234 (1) ◽  
pp. 106-119 ◽  
Author(s):  
D. Alessio Panzica ◽  
Amy S. Findlay ◽  
Rianne Ladesteijn ◽  
J. Martin Collinson
Keyword(s):  
Cell Polarity ◽  
Corneal Epithelium ◽  
Planar Cell Polarity ◽  
The Core ◽  
Polarity Gene

scholarly journals Connectomics of the zebrafish's lateral-line neuromast reveals wiring and miswiring in a simple microcircuit

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eliot Dow ◽  
Adrian Jacobo ◽  
Sajjad Hossain ◽  
Kimberly Siletti ◽  
A J Hudspeth
Keyword(s):  
Hair Cell ◽  
Lateral Line ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Developmental Stages ◽  
Notch Signaling Pathway ◽  
Nerve Fibers ◽  
Directional Sensitivity ◽  
Efferent Nerve ◽  
Polarity Gene

The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity gene vangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.

scholarly journals Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear

2014 ◽  
Vol 395 (1) ◽  
pp. 62-72 ◽  
Author(s):  
Chonnettia Jones ◽  
Dong Qian ◽  
Sun Myoung Kim ◽  
Shuangding Li ◽  
Dongdong Ren ◽  
...  
Keyword(s):  
Inner Ear ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Functional Homolog ◽  
Polarity Gene

scholarly journals Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction

2013 ◽  
Vol 200 (2) ◽  
pp. 219-233 ◽  
Author(s):  
Keisuke Kamimura ◽  
Kohei Ueno ◽  
Jun Nakagawa ◽  
Rie Hamada ◽  
Minoru Saitoe ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Neuromuscular Junction ◽  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Nuclear Import ◽  
Heparan Sulfate Proteoglycans ◽  
Down Regulation ◽  
Bidirectional Signaling ◽  
Synaptic Boutons ◽  
Signaling Activity

Heparan sulfate proteoglycans (HSPGs) play pivotal roles in the regulation of Wnt signaling activity in several tissues. At the Drosophila melanogaster neuromuscular junction (NMJ), Wnt/Wingless (Wg) regulates the formation of both pre- and postsynaptic structures; however, the mechanism balancing such bidirectional signaling remains elusive. In this paper, we demonstrate that mutations in the gene of a secreted HSPG, perlecan/trol, resulted in diverse postsynaptic defects and overproduction of synaptic boutons at NMJ. The postsynaptic defects, such as reduction in subsynaptic reticulum (SSR), were rescued by the postsynaptic activation of the Frizzled nuclear import Wg pathway. In contrast, overproduction of synaptic boutons was suppressed by the presynaptic down-regulation of the canonical Wg pathway. We also show that Trol was localized in the SSR and promoted postsynaptic accumulation of extracellular Wg proteins. These results suggest that Trol bidirectionally regulates both pre- and postsynaptic activities of Wg by precisely distributing Wg at the NMJ.

Sign in / Sign up

Export Citation Format

Share Document