A Motor Function for Drosophila Gemin3 Figure 8. Pupal developmental defects associated with Gemin3 disruption in mesoderm and larval muscles. Compared to wild-type, flies expressing gemin3DN in mesoderm and larval somatic muscles display several aberrations at metamorphosis. (A–D) Ventral view showing that how-GAL4&gemin3DN flies are ‘headless’ as a result of failed head eversion and exhibit elongated pupae as well as shorten wings. (E–F) Dorsal view showing that in how-GAL4&gemin3DN flies the abdomen remains elongated as in the larval stage, and red-pigmented eye discs are often clearly visible within the thorax, denoted by an arrow. The abdomen shows normal segmentation as discerned by the complete bristle pattern on the abdominal tergites. (G–I) Dorsal view showing that compared to controls, in how-GAL4&gemin3DN flies, leg discs have everted but the appendages do not appear fully elongated compared to those of controls (arrowhead). In (C–I), the puparium was removed whilst the pupal cuticle was left intact. Pupae were photographed at the same magnification at approximately 3 days following puparium formation. doi:10.1371/journal.pgen.1000265.g008 mice. However, while Gemin3-null mice died at an early embryonic stage, gemin3 mutant flies exhibit delayed lethality, which probably results from maternal contribution of the gemin3 transcript. In a separate study in female ovaries, we observed severe defects in nurse cells and oocytes when gemin3 is disrupted in germline cells (RJC, KED, and JLL, unpublished data). Motor Function of Gemin3: Pre- or Post-Synaptic? The earliest clues pointing towards a motor function were a progressive loss of mobility and consequent long and thin puparia when Gemin3 function is lost. Similar phenotypes have previously been observed in mutants with disrupted Mlp84B, a muscle sarcomeric protein [30], or Tiggrin, an extracellular matrix ligand for the position-specific 2 integrins [31]. We also observe that gemin3 mutants have an overgrown NMJ though these could be a secondary response to the progressive loss of muscle power. The size ratio of NMJs to muscles is reduced when gemin3 is overexpressed raising the possibility that Gemin3 might also play a role in synaptic growth. The requirement of Gemin3 in mesoderm and larval muscles for adult viability suggests a function of Gemin3 at the post- synaptic side. Based on the tissue-specific phenotypes uncovered, such a function is critical for pupal metamorphic changes and flight muscles. However, another possible explanation is that an earlier and wider disruption of Gemin3 by mesodermal-related drivers is responsible for the lethality, while late and local disruption of Gemin3 by neuroectodermal-related drivers causes milder phenotypes. More studies on the expression details of Gemin3 in pre- and post-synaptic tissues would help to distinguish those views. Relationship between Gemin3 and SMN Studies in vertebrate systems, in vitro and in vivo, have shown that Gemin3 directly binds to SMN [24]. A recent study in Drosophila culture cells [23] and this study in fly tissues confirm that the interaction between Gemin3 and SMN is conserved from fly to human. PLoS Genetics | www.plosgenetics.org 8 November 2008 | Volume 4 | Issue 11 | e1000265