Matrix metalloproteinase 1 modulates invasive behavior of tracheal branches during entry into Drosophila flight muscles.

Julia Sauerwald,Wilko Backer,Frank Schnorrer,Till Matzat,Stefan Luschnig

doi:10.7554/elife.48857

Julia Sauerwald, Wilko Backer + Show 3 more

Open Access

https://doi.org/10.7554/elife.48857

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Abstract

Tubular networks like the vasculature extend branches throughout animal bodies, but how developing vessels interact with and invade tissues is not well understood. We investigated the underlying mechanisms using the developing tracheal tube network of Drosophila indirect flight muscles (IFMs) as a model. Live imaging revealed that tracheal sprouts invade IFMs directionally with growth-cone-like structures at branch tips. Ramification inside IFMs proceeds until tracheal branches fill the myotube. However, individual tracheal cells occupy largely separate territories, possibly mediated by cell-cell repulsion. Matrix metalloproteinase 1 (MMP1) is required in tracheal cells for normal invasion speed and for the dynamic organization of growth-cone-like branch tips. MMP1 remodels the CollagenIV-containing matrix around branch tips, which show differential matrix composition with low CollagenIV levels, while Laminin is present along tracheal branches. Thus, tracheal-derived MMP1 sustains branch invasion by modulating the dynamic behavior of sprouting branches as well as properties of the surrounding matrix.

Highlights

Indirect flight muscles (IFMs) of flying insects display the highest known metabolic rates in the animal kingdom (Weis-Fogh, 1964)
Through live imaging of muscle tracheation, we found that tracheal cells invade the muscle directionally with growth cone-like structures at branch tips
Using a tissuespecific RNAi-based approach to identify factors required for branch invasion, we found that Matrix metalloproteinase 1 (MMP1) activity is required in tracheal cells for normal speed of invasion and for the dynamic organization of growth-cone-like structures at migrating branch tips

Summary

Introduction

Indirect flight muscles (IFMs) of flying insects display the highest known metabolic rates in the animal kingdom (Weis-Fogh, 1964). Each adult IFM is approximately 1 mm long and 100 mm wide (Spletter et al, 2018) and contains about 1000 nuclei (Rai and Nongthomba, 2013) To supply these large muscles with sufficient oxygen, an extensive network of gas-filled tracheal tubes superficially enwraps the IFMs, and invades the myotube interior. The T-tubule system is a network of tubular longitudinal and transversal membranes that extend around each sarcomere and are required for excitation-contraction coupling (Razzaq et al, 2001) It is continuous with the plasma membrane and was proposed to provide entry points for invasion of tracheal branches into the IFMs (Peterson and Krasnow, 2015). We found that MMP1 remodels the Collagen IV-containing ECM around invading branch tips, suggesting that tracheal-derived MMP1 sustains branch invasion by modulating the properties of the surrounding matrix

Results

Discussion

Materials and methods

Funding Funder Boehringer Ingelheim Fonds