Abstract
Muscle development is a multistep process that involves cell specification, myoblast fusion, myotube migration, and attachment to the tendons. In spite of great efforts trying to understand the basis of these events, little is known about the molecular mechanisms underlying myotube migration. Knowledge of the few molecular cues that guide this migration comes mainly from studies in Drosophila. The migratory process of Drosophila embryonic muscles involves a first phase of migration, where muscle progenitors migrate relative to each other, and a second phase, where myotubes migrate searching for their future attachment sites. During this phase, myotubes form extensive filopodia at their ends oriented preferentially toward their attachment sites. This myotube migration and the subsequent muscle attachment establishment are regulated by cell adhesion receptors, such as the conserved proteoglycan Kon-tiki/Perdido. Laminins have been shown to regulate the migratory behavior of many cell populations, but their role in myotube migration remains largely unexplored. Here, we show that laminins, previously implicated in muscle attachment, are indeed required for muscle migration to tendon cells. Furthermore, we find that laminins genetically interact with kon-tiki/perdido to control both myotube migration and attachment. All together, our results uncover a new role for the interaction between laminins and Kon-tiki/Perdido during Drosophila myogenesis. The identification of new players and molecular interactions underlying myotube migration broadens our understanding of muscle development and disease.
Highlights
Muscle development is a complex process where a series of cellular events need to be timely coordinated to render functional contracting muscles
Since laminins play a role in embryonic cell migration; are required for muscle-tendon attachment (Martin et al, 1999; Urbano et al, 2009); bind the tendon expressed αPS1βPS integrin (Gotwals et al, 1994), which might play a role in early events of the formation of the myotendinous junction (MTJ) (Roote and Zusman, 1995; Estrada et al, 2007); and genetically interact with Kon-tiki/ Perdido (Kon) (Wolfstetter and Holz, 2012), we aimed to study the potential role of laminins in myotube migration and its cooperation with Kon during this process
Since loss of function of either kon and LanB1 showed myospheres, we studied their cooperation during MTJ development by performing genetic interaction experiments
Summary
Muscle development is a complex process where a series of cellular events need to be timely coordinated to render functional contracting muscles. At late stages of muscle development, once muscle and tendons have physically contacted, final adhesion takes place by the assembly of a robust hemiadherens junction between these cells (Schnorrer and Dickson, 2004; Schweitzer et al, 2010). This junction contains cell adhesion receptors and extracellular matrix (ECM) proteins (Valdivia et al, 2017), and the absence of these types of molecules leads to the formation of rounded muscles or myospheres. The formation of myospheres has been traditionally attributed to defects in the stabilization of the MTJ, defects in the earlier process of muscle migration towards tendon cells can lead to the same phenotype (Kramer et al, 2001; Swan et al, 2004)
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