Muscle adhesion

Morphological aspects of somatic muscle and heart formation as well as the underlying gene activities are conserved between vertebrates and Drosophila. Each muscle fiber originates from a distinct muscle founder cell that is determined by specific combinations of transcription factors. Subsequently, the founder cells form syncitial myotubes by the fusion with specific competent mesodermal cells. In parallel, the syncitial myotube extend by the formation of polar growth cone-like structures at their polar ends. As a result, myotubes elongate and extend along the epidermis towards their apodemes at the segment borders. The approaching myotube secretes Vein, an EGF that accomplishes the final differentiation of those apodemes that are directly contacted by myotubes. After contacting each other, myotubes and apodemes start their final differentiation, a process characterized by the expression of proteins of the contractile apparatus.

Each muscle originate from a single muscle founder (left), fuses with myoblasts (center) and grow towards its later attachment sites within the epidermis (right)

The anchorage of the muscles is assured by integrin proteins. Integrins are heterodimeric proteins which in Drosophila consists of specific a-subunits that dimerise with a common b-subunit in most of the tissues. In case of the muscle apodeme anchorage the apodemes and muscle express the complementary set of the so called “position specific” PS-Integrins. However, although this complementary set of PS-Integrins is required for the attachment between many different cell types the Integrin proteins do not interact directly with each other in the intercellular space. Instead, the Integrin dimers interact with specific proteins of the extra cellular matrix (ECM). We have shown that the muscle-specific Integrins interact with Thrombospondin, which is expressed and secreted from the apodeme cells. This interaction is one of three characterized interactions that are required in a combinatory way to finally anchor the muscles at the epidermal apodemes. However, based on the strength of the phenotype, Thrombospondin seems to be the most important anchoring partners of the Integrins at the apodemes. Furthermore, we could show that Thrombospondin expression is controlled early in parallel to stripe via competing Wingless and Hedgehog signaling but late in the differentiated apodeme cells directly by Stripe activity. Therefore, Thrombospondin is one of the genes that are directly regulated downstream of stripe being essential for muscle within the apodemes.

Each muscle is attached to epidermal apodemes sites via Integrins bound to the ECM-protein Thrombospondin
secreted from the apodemes

To withstand the contracting forces of the muscles, the apodemes are characterized by an intensive network of cytoskeleton that transfer the forces of the muscles through the apodeme cells towards the cuticule that is stably attached towards the basal site of the apodemes. Therefore, many genes required for muscle anchorage encode proteins of this highly complex cytoplasmic network.