Misregulation of Drosophila Sidestep Leads to Uncontrolled Wiring of the Adult Neuromuscular System and Severe Locomotion Defects

Abstract

Holometabolic organisms undergo extensive remodelling of their neuromuscular system during metamorphosis. Relatively, little is known whether or not the embryonic guidance of molecules and axonal growth mechanisms are re-activated for the innervation of a very different set of adult muscles. Here, we show that the axonal attractant Sidestep (Side) is re-expressed during Drosophila metamorphosis and is indispensable for neuromuscular wiring. Mutations in side cause severe innervation defects in all legs. Neuromuscular junctions (NMJs) show a reduced density or are completely absent at multi-fibre muscles. Misinnervation strongly impedes, but does not completely abolish motor behaviours, including walking, flying, or grooming. Overexpression of Side in developing muscles induces similar innervation defects; for example, at indirect flight muscles, it causes flightlessness. Since muscle-specific overexpression of Side is unlikely to affect the central circuits, the resulting phenotypes seem to correlate with faulty muscle wiring. We further show that mutations in beaten path Ia (beat), a receptor for Side, results in similar weaker adult innervation and locomotion phenotypes, indicating that embryonic guidance pathways seem to be reactivated during metamorphosis.

The effect of Drosophila attP40 background on the glomerular organization of Or47b olfactory receptor neurons

“…To identify the molecular players contributing to the glomerular organization of the ORNs, we genetically screened genes encoding cell adhesion molecules whose expression levels increase over pupal development in the antennae ( Barish et al 2018 ). Among these, beat and side gene families drew our attention because they encode the Ig superfamily proteins, form a heterophilic interacting protein network, and have been previously revealed to be involved in neuronal adhesion ( Fambrough and Goodman 1996 ; Pipes et al 2001 ; Sink et al 2001 ; de Jong et al 2005 ; Siebert et al 2009 ; Özkan et al 2013 ; Li et al 2017 ; Kinold et al 2021 ). We obtained a collection of transgenic UAS-RNAi lines from TriP library deposited at the Bloomington Drosophila Stock Center (BDSC) and crossed these lines with an established recombinant chromosome containing four different Or promoter-driven GAL4 transgenes ( Or47a-GAL4 , Or47b-GAL4 , Or23a-GAL4 , Gr21a-GAL4 , 4xOr-GAL4 for short, Fig.…”

The effect ofDrosophila attP40background on the glomerular organization of Or47b olfactory receptor neurons

“…To identify the molecular players contributing to the glomerular organization of the ORNs, we genetically screened genes encoding cell adhesion molecules whose expression levels increase over pupal development in the antennae (BARISH et al 2018). Among these, beat and side gene families drew our attention because they encode the Ig superfamily proteins, form a heterophilic interacting protein network, and have been previously revealed to be involved in neuronal adhesion (FAMBROUGH AND GOODMAN 1996;PIPES et al 2001;SINK et al 2001;DE JONG et al 2005;SIEBERT et al 2009;ÖZKAN et al 2013;LI et al 2017;KINOLD et al 2021). We obtained a collection of transgenic UAS-RNAi lines from TriP library deposited at the Bloomington Drosophila Stock Center (BDSC) and crossed these lines with an established recombinant chromosome containing four different Or promoter-driven GAL4 transgenes (Or47a-GAL4, Or47b-GAL4, Or23a-GAL4, Gr21a-GAL4, 4xOr-GAL4 for short, Figure 1A-D) together with a UAS-Syt.GFP reporter.…”