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

Hermann Aberle,Jaqueline C Kinold,Marcel Brenner

doi:10.3389/fncir.2021.658791

Hermann Aberle, Jaqueline C Kinold + Show 1 more

Open Access

https://doi.org/10.3389/fncir.2021.658791

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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.

Highlights

Excitatory motor neurons in the central nervous system and their peripheral target muscles are connected in a precise wiring pattern
Motor axon guidance phenotypes occurring in sidestep mutant embryos are irreversible and lead to permanent innervation errors in larvae (Siebert et al, 2009; Kinold et al, 2018)
We would expect that Side is reexpressed during metamorphosis but since it has 7 paralogs (Li et al, 2017); it is possible that other family members replace Side, functionally in pupae

Summary

Introduction

Excitatory motor neurons in the central nervous system and their peripheral target muscles are connected in a precise wiring pattern. This neuromuscular system is established during embryonic development and it is essential for all the coordinated motor behaviours, later in life. While the molecular functions and mutant phenotypes of these guidance molecules have been well-characterised during embryonic development in the last decades (Tessier-Lavigne and Goodman, 1996; Bashaw and Klein, 2010), less is known about their functions during metamorphosis of holometabolous organisms. Abdominal muscles develop from clusters of persistent Twist-expressing cells associated with larval segmental nerves (Currie and Bate, 1991). The dorsal longitudinal flight muscles develop from a few persisting larval muscles that fuse with the surrounding muscle precursors (myoblasts) (Fernandes et al, 1991)

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