Embryonic somatic muscle development in Drosophila is a multistep process that initiates with the specification of founder cells from a field of myogenic competent cells in the mesoderm

INTRODUCTION The transcriptional regulatory networks that direct muscle precursor cell specification and the expression of muscle structural genes have been well defined. However, the possible post-transcriptional contribution to mesoderm development is only beginning to come to light (Biedermann et al., 2010; Toledano-Katchalski et al., 2007; Yarnitzky et al., 1998). The unique properties of Drosophila, including external development and an extensive array of genetic tools, have allowed the discrete cellular processes directing muscle development to be dissected in detail (Guerin and Kramer, 2009a; Schejter and Baylies, 2010; Schnorrer and Dickson, 2004). Embryonic somatic muscle development in Drosophila is a multistep process that initiates with the specification of founder cells from a field of myogenic competent cells in the mesoderm (Carmena et al., 1995; Jagla et al., 1998). Founder cells express a unique set of muscle identity genes, encoding transcription factors, that direct differentiation into one of 30 somatic muscles (de Joussineau et al., 2012). Once specified, muscle founders begin the process of migration and elongation that can be divided into three phases (Schnorrer and Dickson, 2004). During the first phase, founder cells migrate to their correct position within the segment. The second phase begins when the founder cells initiate myoblast fusion and form polarized myotubes that elongate along a single axis. The myotubes then form extensive filopodia in the direction of initial polarity, presumably in response to guidance cues from tendon cells in the overlying epidermis (Guerin and Kramer, 2009a; Schnorrer and Dickson, 2004). The center of the myotube remains localized while the ends of the myotube elongate towards their respective muscle-attachment sites (Schnorrer and Dickson, 2004). The final phase of elongation initiates when the myotube ends reach their muscle attachment sites and filopodia no longer form. The myotube then localizes integrin-mediated adhesion complexes with the overlying tendon cells to establish strong myotendinous junctions (Schejter and Baylies, 2010). The mechanisms that control myotube elongation during somatic muscle morphogenesis are poorly understood. Slit is the single guidance molecule known to direct both myotube elongation and target site recognition, but loss of Slit modestly affects the elongation of only a subset of myotubes (Kramer et al., 2001). Nascent myotubes must undergo extensive cytoskeletal rearrangements during elongation, and recent work has focused on the role of microtubule dynamics in this process (Folker et al., 2012; Guerin and Kramer, 2009b). Tumbleweed (Tum) is a Rac family GTPase-activating protein that becomes localized to the nuclear periphery via its association with the microtubule-associated protein Pavarotti (Pav). Loss of pav or tum disrupts microtubule polarity and polarized growth, mislocalizes the minus-end microtubule nucleator γ-tubulin and causes modest myotube elongation defects (Guerin and Kramer, 2009b). A second regulator of microtubule dynamics, Dynein heavy chain (Dhc64C), is also required for myotube elongation but its role is restricted to the final stages of elongation (Folker et al., 2012). Although microtubule dynamics plays a key role in the process, the mechanisms that initiate myotube elongation and the downstream targets of intracellular messenger proteins, such as Tum, remain largely unknown. The cellular events that regulate myotube morphology are distinct from the molecular processes that direct terminal differentiation and structural gene expression. Embryos defective in myoblast fusion express Myosin Heavy Chain (MHC) in unfused mononucleate 1Department of Molecular Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA. 2Department of Integrative Biology, University of Colorado Denver, Denver, CO 80204, USA. 3Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.