Document Detail


Analysis of synaptic growth and function in Drosophila with an extended larval stage.
MedLine Citation:
PMID:  23035089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Drosophila larval neuromuscular junction (NMJ) is a powerful system for the genetic and molecular analysis of neuronal excitability, synaptic transmission, and synaptic development. However, its use for studying age-dependent processes, such as maintenance of neuronal viability and synaptic stability, are temporally limited by the onset of pupariation and metamorphosis. Here we characterize larval NMJ growth, growth regulation, structure, and function in a developmental variant with an extended third instar (ETI). RNAi-knockdown of the prothoracicotropic hormone receptor, torso, in the ring gland of developing larvae leaves the timing of first and second instar molts largely unchanged, but triples duration of the third instar from 3 to 9.5 d (McBrayer et al., 2007; Rewitz et al., 2009). During this ETI period, NMJs undergo additional growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGFβ/BMP pathway. NMJ growth during the ETI period occurs via addition of new branches, satellite boutons, and interstitial boutons, and continues even after muscle growth levels off. Throughout the ETI, organization of synapses and active zones remains normal, and synaptic transmission is unchanged. These results establish the ETI larval system as a viable model for studying motor neuron diseases and for investigating time-dependent effects of perturbations that impair mechanisms of neuroprotection, synaptic maintenance, and response to neural injury.
Authors:
Daniel L Miller; Shannon L Ballard; Barry Ganetzky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13776-86     Citation Subset:  IM    
Affiliation:
Laboratory of Genetics and Institute on Aging, University of Wisconsin, Madison, Wisconsin 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Drosophila Proteins / antagonists & inhibitors,  biosynthesis,  genetics,  physiology
Drosophila melanogaster / growth & development*,  physiology
Insect Hormones / physiology
Insect Proteins / antagonists & inhibitors,  genetics
Larva
Mixed Function Oxygenases / genetics,  physiology
Molting / physiology
Nervous System / growth & development*
Neuromuscular Junction / growth & development*
Presynaptic Terminals / physiology*,  ultrastructure
RNA Interference
RNA, Small Interfering / pharmacology
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors,  biosynthesis,  genetics
Receptors, Steroid / antagonists & inhibitors,  genetics
Time Factors
Grant Support
ID/Acronym/Agency:
F32 NS067843/NS/NINDS NIH HHS; F32 NS067843/NS/NINDS NIH HHS; R01 AG033620/AG/NIA NIH HHS; R01 AG033620/AG/NIA NIH HHS; R01 NS015390/NS/NINDS NIH HHS; R01 NS015390/NS/NINDS NIH HHS; R21 NS078342/NS/NINDS NIH HHS; R21 NS078342/NS/NINDS NIH HHS; T32 AG000213/AG/NIA NIH HHS; T32 AG000213/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Drosophila Proteins; 0/Insect Hormones; 0/Insect Proteins; 0/RNA, Small Interfering; 0/Receptors, Steroid; 0/ecdysone receptor; 0/ecdysone receptor A, insect; 61583-57-1/prothoracicotropic hormone; EC 1.-/Mixed Function Oxygenases; EC 1.-/phantom protein, Drosophila; EC 2.7.1.-/torso protein, Drosophila; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases
Comments/Corrections

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