Type ID unconventional myosin controls left–right asymmetry in Drosophila

Abstract

Breaking left-right symmetry in Bilateria embryos is a major event in body plan organization that leads to polarized adult morphology, directional organ looping, and heart and brain function. However, the molecular nature of the determinant(s) responsible for the invariant orientation of the left-right axis (situs choice) remains largely unknown. Mutations producing a complete reversal of left-right asymmetry (situs inversus) are instrumental for identifying mechanisms controlling handedness, yet only one such mutation has been found in mice (inversin) and snails. Here we identify the conserved type ID unconventional myosin 31DF gene (Myo31DF) as a unique situs inversus locus in Drosophila. Myo31DF mutations reverse the dextral looping of genitalia, a prominent left-right marker in adult flies. Genetic mosaic analysis pinpoints the A8 segment of the genital disc as a left-right organizer and reveals an anterior-posterior compartmentalization of Myo31DF function that directs dextral development and represses a sinistral default state. As expected of a determinant, Myo31DF has a trigger-like function and is expressed symmetrically in the organizer, and its symmetrical overexpression does not impair left-right asymmetry. Thus Myo31DF is a dextral gene with actin-based motor activity controlling situs choice. Like mouse inversin, Myo31DF interacts and colocalizes with beta-catenin, suggesting that situs inversus genes can direct left-right development through the adherens junction.

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

“…Evidence has been presented that nonmuscle myosins function in Drosophila in organizing the cytoskeleton during morphogenesis and in controlling left-right asymmetry (Blake et al, 1998(Blake et al, , 1999Speder et al, 2006). In summary, our study suggests that NMHC-IIB within the cytoskeleton has a role in laterality and mammalian mouse heart morphogenesis during looping.…”

Roles of Type I Myosins in Drosophila Handedness

“…1C and D and Table 1). Spéder et al 13 reported that the laterality of the spermiduct and genitalia in the adult of Myo31DF homozygote was also reversed (review on the roles of Myo31DF in the asymmetry of the adult genitalia www.landesbioscience.com…”

Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development inDrosophila

“…These findings indicate that Myo95E 1 and Myo95E 2 are null alleles of Myo95E. We used the Myo95E 1 allele in subsequent studies, because it had a larger deletion than Myo95E 2 ( Figure 1C).Myo31DF or Myo61F homozygous mutant flies were previously reported to be viable and fertile (Hozumi et al 2006;Speder et al 2006;Hegan et al 2007). Our finding that the Myo61F 1 or Myo95E 1 homozygotes were also viable and fertile (data not shown) combined with the earlier data suggests that all class I myosins are dispensable for survival in Drosophila, if their functions are disrupted separately.…”

“…These results demonstrated that class I myosins are not essential for survival itself, but are required for optimal hatching and survival rates, and thus are important mediators in Drosophila, at least under our experimental conditions. Differential expression of Myo31DF, Myo61F, and Myo95E during embryogenesis Myo31DF and Myo61F mRNAs and their protein products are detected in the gut epithelium and genital disc (Morgan et al 1995;Hozumi et al 2006;Speder et al 2006;Petzoldt et al 2012). To gain insight into the tissue-specific roles and functional redundancy of the three class I myosins in the LR asymmetric development of the embryonic gut, we analyzed their expression in embryos, using in situ hybridization.…”