Slowdown promotes muscle integrity by modulating integrin-mediated adhesion at the myotendinous junction.

The correct assembly of the myotendinous junction (MTJ) is crucial for proper muscle function. In Drosophila, this junction comprises hemi-adherens junctions that are formed upon arrival of muscles at their corresponding tendon cells. The MTJ mainly comprises muscle-specific alphaPS2betaPS integrin receptors and their tendon-derived extracellular matrix ligand Thrombospondin (Tsp). We report the identification and functional analysis of a novel tendon-derived secreted protein named Slowdown (Slow). Homozygous slow mutant larvae exhibit muscle or tendon rupture, sluggish larval movement, partial lethality, and the surviving adult flies are unable to fly. These defects result from improper assembly of the embryonic MTJ. In slow mutants, Tsp prematurely accumulates at muscle ends, the morphology of the muscle leading edge changes and the MTJ architecture is aberrant. Slow was found to form a protein complex with Tsp. This complex is biologically active and capable of altering the morphology and directionality of muscle ends. Our analysis implicates Slow as an essential component of the MTJ, crucial for ensuring muscle and tendon integrity during larval locomotion.

Acidic peptide hydrogel scaffolds enhance calcium phosphate mineral turnover into bone tissue.

Designed peptides may generate molecular scaffolds in the form of hydrogels to support tissue regeneration. We studied the effect of hydrogels comprising ß-sheet-forming peptides rich in aspartic amino acids and of tricalcium phosphate (ß-TCP)-loaded hydrogels on calcium adsorption and cell culture in vitro, and on bone regeneration in vivo. The hydrogels were found to act as efficient depots for calcium ions, and to induce osteoblast differentiation in vitro. In vivo studies on bone defect healing in rat distal femurs analyzed by microcomputerized tomography showed that the peptide hydrogel itself induced better bone regeneration in comparison to non-treated defects. A stronger regeneration capacity was obtained in bone defects treated with ß-TCP-loaded hydrogels, indicating that the peptide hydrogels and the mineral act synergistically to enhance bone regeneration. In vivo regeneration was found to be better with hydrogels loaded with porous ß-TCP than with hydrogels loaded with non-porous mineral. It is concluded that biocompatible and biodegradable matrices, rich in anionic moieties that efficiently adsorb calcium ions while supporting cellular osteogenic activity, may efficiently promote ß-TCP turnover into bone mineral.

A screen for tendon-specific genes uncovers new and old components involved in muscle-tendon interaction.

The formation of complex tissues requires the assembly of distinct cell types that often migrate over long distances in order to interact with each other and establish a functional tissue. The establishment of the contractile tissue in the Drosophila embryo has been used as a model system in which to study how the interplay between distinct cell types results in a complex, functioning tissue. The Drosophila contractile tissue is composed of multi-nucleated muscle cells that are attached to individual specialized ectodermal cells, named tendon cells, at each end. The tendon cells are anchored to the cuticle external skeleton on their apical side and form integrin-dependent myotendinous junctions at their basal end. In order for the complex muscle-pattern to form, muscles must undergo several tightly regulated processes: They need to migrate towards their respective tendon cells, arrest migration upon arrival to the tendon cells and form integrin-mediated muscle-tendon junctions (MTJs) in an accurate manner that would guarantee appropriate muscle function.(1,2) The regulation of many of these events is still poorly understood, driving us to search for novel mechanisms that enable the functionality of the contractile tissue.