Myoblast Fusion

Funding Source: DFG PA517/15-1

Principle Investigator: Achim Paululat & Maik Drechsler with Jonas Olbrich

Dynamics of Myoblast Fusion and the Role of the APC/C protein Fizzy-related Somatic muscles of all higher organisms arise during embryogenesis by the coordinated fusion of individual myoblasts into larger, syncytial muscle fibres. We identified the APC/CFzr as a novel key player during myoblast fusion. Embryos mutant for fzr exhibit an arrest of myoblast fusion, and display a  reduction of  muscle fibres as well as an access of unfused myoblasts by the end of embryogenesis. We aim to identify and understand the mechanism of the APC/CFzr on the fusion process by applying state-of-the art light- and electron microscopy as well as proteomic approaches.

Picture A shows a Drosophila embryo stained for all the 300 muscles. Muscles allow the larvae to crawl around. Muscles are innervated by motoneurons to allow controlled locomotion. Picture B shows individual larval muscles stained for actin filaments and the nuclei. Note, that each muscle contains several nuclei. Drosophila muscles are syncytial, like the muscles in the human body.

This pictures on the right shows, how syncytial muscles are formed: by cell-cell fusion. A-D illustrates a series of fusion events, leading to membrane break down and the fusion of two myoblasts into one. Transmission electrone micrographs.

To the right you see staining of a healthy embryo (wild-type) (E) and staining of a mutant embryo (F). This is a fizzy-related mutant in which the myoblasts fail to fuse.

The project aims to elucide the precise role of the Fizzy-related protein, which is one of the components of the cell´s APC/C complex (degeneration machinery) for cell cell fusion.