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Functional diversification of homologous neuronal microcircuits is a widespread feature observed across brain regions, as well as across species, while its molecular and developmental mechanisms remain largely unknown. We address this question in Drosophila larvae by focusing on segmentally homologous Wave command-like neurons, which diversify their wiring and function in a segment-specific manner. Anterior Wave (a-Wave) neurons extend axons anteriorly and connect to circuits inducing backward locomotion, whereas posterior Wave (p-Wave) neurons extend axons posteriorly and trigger forward locomotion. Here, we show that Frizzled receptors DFz2 and DFz4, together with the DWnt4 ligand, regulate the segment-specific Wave axon projection. DFz2 knockdown (KD) not only reroutes Wave axons to posterior neuromeres but also biases its motor command to induce forward instead of backward locomotion as tactile response. Thus, segment-specific axon guidance diversifies the function of homologous command neurons in behavioral regulation. Since control of anterior-posterior (A-P) axon guidance by Wnt/Fz signaling is evolutionarily conserved, our results reveal a potentially universal molecular principle for formation and diversification of the command system in the nerve cord. Furthermore, this work indicates that sensorimotor transduction can be rerouted by manipulating a single gene in a single class of neurons, potentially facilitating the evolutionary flexibility in action selection.
Pubmed ID: 40996811
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View all literature mentionsServes Drosophila research community by collecting and distributing DNA clones and vectors; collecting and distributing Drosophila cell lines; developing and testing genomics technologies for use in Drosophila and assisting members of the research community in their use.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-smo.RNAi}2 P{UAS-smo.RNAi}8/CyO, P{Wee-P.ph0}2 from BDSC.
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets Mouse Drosophila fasciclin II
View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets green fluorescent protein (YP_002302326)
View all literature mentionsThis monoclonal targets Bruchpilot
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Brp
View all literature mentionsThis monoclonal targets Repo; Reversed polarity protein
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets SOCS3
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Horseradish Peroxidase
View all literature mentionsThis monoclonal targets V5 Tag
View all literature mentionsThis monoclonal targets elav Drosophila protein; embryonic lethal abnormal vision
View all literature mentionsDrosophila melanogaster with name w[1118] Wnt5[400] P{ry[+t7.2]=neoFRT}19A from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR77H11-lexA}attP40/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; Wnt4[C1]/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.GL01472}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; TI{w[+mW.hs]=TI}Wnt6[KO] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] P{y[+t7.7] w[+mC]=R57C10-FLPL}su(Hw)attP8; P{y[+t7.7] w[+mC]=10xUAS(FRT.stop)myr::smGdP-OLLAS}attP2 PBac{y[+mDint2] w[+mC]=10xUAS(FRT.stop)myr::smGdP-HA}VK00005 P{10xUAS(FRT.stop)myr::smGdP-V5-THS-10xUAS(FRT.stop)myr::smGdP-FLAG}su(Hw)attP1 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04172}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR60G09-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01918}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02287}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; PBac{y[+mDint2] w[+mC]=UAS-CD4-tdGFP}VK00033 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{Trojan-GAL4.2}Wnt4[MI03717-TG4.2] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GLC01626}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; TI{w[+mW.hs]=TI}wntD[KO1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01308}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS05675}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05864}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR77H11-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=UAS-mCherry.VALIUM10}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118] from BDSC.
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