Founder cells regulate fiber number but not fiber formation during adult myogenesis in Drosophila

Abstract

During insect myogenesis, myoblasts are organized into a pre-pattern by specialized organizer cells. In the Drosophila embryo, these cells have been termed founder cells and play important roles in specifying muscle identity and in serving as targets for myoblast fusion. A group of adult muscles, the dorsal longitudinal (flight) muscles, DLMs, is patterned by persistent larval scaffolds; the second set, the dorso-ventral muscles, DVMs is patterned by mono-nucleate founder cells (FCs) that are much larger than the surrounding myoblasts. Both types of organizer cells express Dumbfounded, which is known to regulate fusion during embryonic myogenesis. The role of DVM founder cells as well as the DLM scaffolds was tested in genetic ablation studies using the UAS/Gal4 system of targeted transgene expression. In both cases, removal of organizer cells prior to fusion, causes formation of supernumerary fibers, suggesting that cells in the myoblast pool have the capacity to initiate fiber formation, which is normally inhibited by the organizers. In addition to the large DVM FCs, some (smaller) cells in the myoblast pool also express Dumbfounded. We propose that these cells are responsible for seeding supernumerary fibers, when DVM FCs are eliminated prior to fusion. When these cells are also eliminated, myogenesis fails to occur. In the second set of studies, targeted expression of constitutively active Ras(V12) also resulted in the appearance of supernumerary fibers. In this case, the original DVM FCs are present, suggesting alterations in cell fate. Taken together, these data suggest that DVM myoblasts are able to respond to cues other than the original founder cell, to initiate fusion and fiber formation. Thus, the role of the large DVM founder cells is to generate the correct number of fibers, but they are not required for fiber formation itself. We also present evidence that the DVM FCs may arise from the leg imaginal disc.

Multinucleated smooth muscles and mononucleated as well as multinucleated striated muscles develop during establishment of the male reproductive organs of Drosophila melanogaster

“…These muscles are multinucleated and probably arise from fusing FCs and FCMs. In both cases, Duf-positive cells were observed that fused with the myoblasts that were forming aggregates around them and did not express Duf (Atreya and Fernandes, 2008;Dutta et al, 2004;Kozopas and Nusse, 2002;Soler et al, 2004). We observed that multinucleated primary myotubes arrive at the testes and express Duf and/or Sns during their further migration and differentiation between the epithelial layer and basal membrane of the testes.…”

The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis

“…Prominent examples include the thoracic dorsoventral muscles (DVMs), which constitute a second major set of IFMs, and the various groups of abdominal muscles, which are derived from nerve-associated myoblasts Fernandes and Keshishian, 1999;Rivlin et al, 2000;Atreya and Fernandes, 2008). We monitored the development of these different muscle types in Wsp mutant pupae and observed severe defects in the construction of all muscles examined (Fig.…”

“…4I) when Wsp was specifically expressed in the persistent larval templates, under rp298 (duf)-GAL4 (also known as kirre -FlyBase) (Menon and Chia, 2001). Although a previous detailed study concluded that this driver is not active in myoblasts (Atreya and Fernandes, 2008), we again used the GAL80 ts /TARGET system (McGuire et al, 2004) to ensure restriction of GAL4 activity to pupal stages (see Fig. S1 in the supplementary material).…”

Crossveinless and the TGFβ pathway regulate fiber number in theDrosophilaadult jump muscle

“…Scale bar: 400 μm for wing images; 50 μm for paraffin sections. presented by Atreya and Fernandes (Atreya and Fernandes, 2008), although their study did not focus specifically upon TDT development.…”

“…These include the abdominal muscles, where each individual muscle is pre-figured by a cell expressing the canonical founder cell marker, dumbfounded/kirre, usually detected as an enhancer trap termed duf-lacZ, or rp298 (Ruiz-Gomez et al, 2000). Precursors of the adult indirect flight muscles also express duf-lacZ (Dutta et al, 2004), and the ablation of these founder cells significantly disturbs the formation of the DVMs (Atreya and Fernandes, 2008). Interestingly, whereas founders have been observed to prefigure adult muscle development, relatively little is known of the mechanisms responsible for their specification at this stage.…”