Allele Dmel\nwk¹

General Information
Symbol	Dmel\nwk¹	Species	D. melanogaster
Name		FlyBase ID	FBal0154819
Feature type	allele	Associated gene	Dmel\nwk

Allele class
Mutagen	ethyl methanesulfonate
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class
Mutagen	ethyl methanesulfonate (Coyle et al., 2004)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference
Cytology
Phenotypic Data
Phenotypic Class
	neuroanatomy defective (Coyle et al., 2004) neuroanatomy defective \| larval stage (with nwk²) (O'Connor-Giles et al., 2008) neuroanatomy defective \| third instar larval stage (Rodal et al., 2008) neuroanatomy defective \| third instar larval stage (with nwk²) (Rodal et al., 2008) neuroanatomy defective \| third instar larval stage (with nwk^{SH3ab.Scer\UAS}), with Scer\GAL4^elav-C155, nwk² (Rodal et al., 2008, Rodal et al., 2008) neurophysiology defective (Coyle et al., 2004) paralytic \| heat sensitive (Coyle et al., 2004) paralytic \| heat sensitive (with nwk²) (Coyle et al., 2004) paralytic \| heat sensitive (with nwk³) (Coyle et al., 2004) paralytic \| heat sensitive (with nwk⁴) (Coyle et al., 2004) paralytic \| heat sensitive (with nwk⁵) (Coyle et al., 2004) size defective \| third instar larval stage (Rodal et al., 2008)
Phenotype Manifest In
	bouton \| supernumerary (Coyle et al., 2004) embryonic/larval neuromuscular junction \| third instar larval stage (Khuong et al., 2010, Rodal et al., 2008) embryonic/larval neuromuscular junction \| third instar larval stage (with nwk²) (Rodal et al., 2008) neuromuscular junction \| larval stage (Coyle et al., 2004) NMJ bouton \| larval stage \| supernumerary (with nwk²) (O'Connor-Giles et al., 2008) NMJ bouton \| third instar larval stage (Rodal et al., 2008) NMJ bouton \| third instar larval stage (with nwk²) (Rodal et al., 2008)
Detailed Description
	Statement Reference nwk[1] mutant third instar larvae exhibit enlarged neuromuscular junctions. (Khuong et al., 2010) Total bouton number and satellite bouton number at the neuromuscular junction is increased in nwk[1]/nwk[2] larvae compared to controls. (O'Connor-Giles et al., 2008) nwk[1] mutants display synaptic overgrowth. The mean bouton number for segment A3, muscle 6/7 is increased compared to wild type and a greater number of satellite boutons is seen in segments A2-A3, muscle 4. nwk[1]/nwk[2] mutants exhibit an increase in overall bouton number. Expression of nwk[SH3ab.Scer\UAS] under the control of Scer\GAL4[elav-C155] enhances the synaptic overgrowth and increased bouton number phenotypes seen in nwk[1]/nwk[2] third instar larvae. (Rodal et al., 2008) Mutant adults behave normally at room temperature, but lose coordination within 10-40 seconds at 38^oC and undergo seizure-like spasms that gradually diminish until the flies become paralysed within 3 minutes. After a 5 minutes exposure to 38^oC, the mutant flies gradually recover when returned to room temperature, and normal behaviour is fully restored after 5-10 minutes. The number of boutons at neuromuscular junction (NMJ) 6/7 is increased by about 50% in mutant larvae compared to controls and a similar increase in bouton number is also seen at NMJ 4. When normalised to muscle surface area, the bouton number at NMJ 6/7 is about 50% larger than in controls, while at NMJ 4 the bouton number is 22% larger than in controls. The NMJ length/muscle area is increased by about 30% compared to controls. The proportion of branching boutons is increased by 50% at NMJ 6/7 and by 125% at NMJ 4 in mutant larvae compared to controls. There is also a striking increase in the incidence of hyperbranched boutons (those extending 3 or more new branches) compared to wild type; at least one is seen in all NMJs 6/7 and about half of all NMJs 4 in the mutant larvae. Most of these hyperbranched boutons extend 3 new branches, but about 10% extend 4. The mean amplitude of the excitatory junctional current (EJC) at neuromuscular junction 6/7 is reduced by more than 50% compared to wild-type larvae. The amplitude of miniature EJCs (quantal size) is slightly increased and mEJC frequency is slightly elevated compared to wild type. (Coyle et al., 2004)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference nwk¹/nwk² has neuroanatomy defective \| larval stage phenotype, enhanceable by Dap160[+]/Dap160^Δ1 (O'Connor-Giles et al., 2008) nwk¹/nwk² has neuroanatomy defective \| larval stage phenotype, enhanceable by endoA^EY02730/endoA[+] (O'Connor-Giles et al., 2008) nwk¹/nwk² has neuroanatomy defective \| larval stage phenotype, enhanceable by shi[+]/shi¹ (O'Connor-Giles et al., 2008) nwk¹ has neuroanatomy defective \| third instar larval stage phenotype, enhanceable by Cdc42² (Rodal et al., 2008) nwk¹ has size defective \| third instar larval stage phenotype, enhanceable by Cdc42² (Rodal et al., 2008)
Suppressed by
Statement Reference nwk¹/nwk² has neuroanatomy defective \| larval stage phenotype, suppressible by wit^A12/wit[+] (O'Connor-Giles et al., 2008) nwk¹ has neuroanatomy defective \| third instar larval stage phenotype, suppressible by wit^B11/wit^A12 (Rodal et al., 2008) nwk¹ has size defective \| third instar larval stage phenotype, suppressible by wit^B11/wit^A12 (Rodal et al., 2008)
Enhancer of
Statement Reference nwk¹/nwk² is an enhancer of neuroanatomy defective \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008) nwk¹ is an enhancer of neuroanatomy defective \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008) nwk¹ is an enhancer of size defective \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008)
NOT Suppressor of
Statement Reference nwk¹ is a non-suppressor of size defective \| third instar larval stage phenotype of wit^A12 (Rodal et al., 2008)
Phenotype Manifest In
Enhanced by
Statement Reference nwk¹/nwk² has NMJ bouton \| supernumerary \| larval stage phenotype, enhanceable by Dap160[+]/Dap160^Δ1 (O'Connor-Giles et al., 2008) nwk¹/nwk² has NMJ bouton \| supernumerary \| larval stage phenotype, enhanceable by endoA^EY02730/endoA[+] (O'Connor-Giles et al., 2008) nwk¹/nwk² has NMJ bouton \| supernumerary \| larval stage phenotype, enhanceable by shi[+]/shi¹ (O'Connor-Giles et al., 2008) nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, enhanceable by Cdc42² (Rodal et al., 2008) nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, enhanceable by Df(3R)3450/WASp¹ (Khuong et al., 2010) nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, enhanceable by Hsap\PLCD1^{PH.Scer\UAS.T:Avic\GFP-EGFP}/Scer\GAL4^n-syb.PS (Khuong et al., 2010) nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, enhanceable by Scer\GAL4^n-syb.PS/tkv^{Q253D.Scer\UAS.cNb} (Khuong et al., 2010) nwk¹ has NMJ bouton \| third instar larval stage phenotype, enhanceable by wit^B11/wit^A12 (Rodal et al., 2008)
NOT Enhanced by
Statement Reference Hsap\PLCD1^{PH.Scer\UAS.T:Avic\GFP-EGFP}, Scer\GAL4^n-syb.PS, nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, non-enhanceable by Df(3R)3450/WASp¹ (Khuong et al., 2010)
Suppressed by
Statement Reference nwk¹/nwk² has NMJ bouton \| supernumerary \| larval stage phenotype, suppressible by wit^A12/wit[+] (O'Connor-Giles et al., 2008) nwk¹ has embryonic/larval neuromuscular junction \| third instar larval stage phenotype, suppressible by wit^B11/wit^A12 (Rodal et al., 2008) nwk¹ has NMJ bouton \| third instar larval stage phenotype, suppressible by Cdc42² (Rodal et al., 2008)
Enhancer of
Statement Reference nwk¹/nwk² is an enhancer of embryonic/larval neuromuscular junction \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008) nwk¹/nwk² is an enhancer of NMJ bouton \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008) nwk¹ is an enhancer of embryonic/larval neuromuscular junction \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008) nwk¹ is an enhancer of embryonic/larval neuromuscular junction \| third instar larval stage phenotype of Df(3R)3450/WASp¹ (Khuong et al., 2010) nwk¹ is an enhancer of NMJ bouton \| third instar larval stage phenotype of Cdc42² (Rodal et al., 2008)
NOT Enhancer of
Statement Reference nwk¹ is a non-enhancer of embryonic/larval neuromuscular junction \| somatic clone \| third instar larval stage phenotype of tweek²/tweek¹ (Khuong et al., 2010)
NOT Suppressor of
Statement Reference nwk¹ is a non-suppressor of embryonic/larval neuromuscular junction \| third instar larval stage phenotype of wit^A12 (Rodal et al., 2008) nwk¹ is a non-suppressor of NMJ bouton \| third instar larval stage phenotype of wit^A12 (Rodal et al., 2008)
Additional Comments
Genetic Interactions
Statement Reference nwk[1] enhances the overgrown neuromuscular junction phenotype seen in WASp[1]/Df(3R)3450 third instar larvae. WASp[1]/Df(3R)3450 enhances the overgrown neuromuscular junction phenotype seen in homozygous nwk[1] third instar larvae. Expression of tkv[Q253D.Scer\UAS.cNb] under the control of Scer\GAL4[n-syb.PS] enhances the neuromuscular junction overgrowth phenotype seen in nwk[1] third instar larvae. nwk[1] does not enhance the neuromuscular junction overgrowth phenotype seen in tweek[1]/tweek[2] third instar larvae. (Khuong et al., 2010) The increase in total bouton number and satellite bouton number at the neuromuscular junction that is seen in nwk[1]/nwk[2] larvae is enhanced if the larvae are also carrying endoA[EY02730]/+, Dap160[Δ1]/+ or shi[1]/+. wit[A12]/+ suppresses the increase in total bouton number at the neuromuscular junction that is seen in nwk[1]/nwk[2] larvae. (O'Connor-Giles et al., 2008) A wit[A12]/wit[B11] transheterozygous background suppresses the synaptic overgrowth and increased bouton number phenotypes found in nwk[1] homozygous third instar larvae, instead the larvae exhibit reduced synaptic growth and fewer boutons than wild type controls. Cdc42[2] nwk[1] double mutants exhibit more severe synaptic overgrowth and an increased number of boutons and satellite boutons compared to either single mutant. (Rodal et al., 2008)
Xenogenetic Interactions
Statement Reference Expression of Hsap\PLCD1[PH.Scer\UAS.T:Avic\GFP-EGFP] under the control of Scer\GAL4[n-syb.PS] enhances the overgrown neuromuscular junction phenotype seen in nwk[1] third instar larvae. Expression of WASp[1]/Df(3R)3450 does not enhance the enlarged neuromuscular junction phenotype seen when Hsap\PLCD1[PH.Scer\UAS.T:Avic\GFP-EGFP] is expressed under the control of Scer\GAL4[n-syb.PS] in homozygous nwk[1] third instar larvae. (Khuong et al., 2010)
Complementation & Rescue Data
Fails to complement	nwk² (Coyle et al., 2004) nwk³ (Coyle et al., 2004) nwk⁴ (Coyle et al., 2004) nwk⁵ (Coyle et al., 2004)
Partially rescued by	nwk¹/nwk² is partially rescued by nwk^Scer\UAS.cCa (Rodal et al., 2008) nwk¹/nwk² is partially rescued by Scer\GAL4^elav-C155/nwk^ΔC.Scer\UAS (Rodal et al., 2008)
Not rescued by	nwk¹/nwk² is not rescued by nwk^{SH3ab.Scer\UAS} (Rodal et al., 2008) nwk¹/nwk² is not rescued by Scer\GAL4^elav-C155/nwk^{SH3a.Scer\UAS} (Rodal et al., 2008) nwk¹/nwk² is not rescued by Scer\GAL4^elav-C155/nwk^{SH3b.Scer\UAS} (Rodal et al., 2008)
Comments	Expression of nwk[Scer\UAS.cCa] under the control of Scer\GAL4[elav-C155] partially rescues the synaptic overgrowth and increased bouton number phenotypes seen in nwk[1]/nwk[2] third instar larvae. Expression of nwk[SH3a.Scer\UAS] under the control of Scer\GAL4[elav-C155] fails to rescue the synaptic overgrowth and increased bouton number phenotypes in nwk[1]/nwk[2] third instar larvae. Expression of nwk[SH3b.Scer\UAS] under the control of Scer\GAL4[elav-C155] fails to rescue the synaptic overgrowth and increased bouton number phenotypes seen in nwk[1]/nwk[2] third instar larvae. Expression of nwk[SH3ab.Scer\UAS] under the control of Scer\GAL4[elav-C155] enhances the synaptic overgrowth and increased bouton number phenotypes seen in nwk[1]/nwk[2] third instar larvae. Expression of nwk[ΔC.Scer\UAS] under the control of Scer\GAL4[elav-C155] partially rescues the synaptic overgrowth and increased bouton number phenotypes seen in nwk[1]/nwk[2] third instar larvae. (Rodal et al., 2008)
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	nwk (Coyle et al., 2004) nwk¹ (O'Connor-Giles et al., 2008, Khuong et al., 2010, Rodal et al., 2008)
Name Synonym
Secondary FlyBase IDs

References ( 4 )
Research paper	Khuong et al., 2010, Proc. Natl. Acad. Sci. U.S.A. 107(40): 17379--17384 WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling. [FBrf0214154] O'Connor-Giles et al., 2008, Neuron 58(4): 507--518 Nervous wreck interacts with thickveins and the endocytic machinery to attenuate retrograde BMP signaling during synaptic growth. [FBrf0204925] Rodal et al., 2008, J. Neurosci. 28(33): 8316--8325 Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth. [FBrf0205746] Coyle et al., 2004, Neuron 41(4): 521--534 Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila. [FBrf0175021]

Allele Dmel\nwk1

Allele Dmel\nwk¹