Natural reversal of left‐right gut/gonad asymmetry in C. elegans males is independent of embryonic chirality

Abstract

Anatomical left-right (L/R) handedness asymmetry in C. elegans is established in the four-cell embryo as a result of anteroposterior skewing of transverse mitotic spindles with a defined handedness. This event creates a chiral embryo and ultimately an adult body plan with fixed L/R positioning of internal organs and components of the nervous system. While this “dextral” configuration is invariant in hermaphrodites, it can be reversed by physical manipulation of the early embryo or by mutations that interfere with mitotic spindle orientation, which leads to viable, mirror-reversed (sinistral) animals. During normal development of the C. elegans male, the gonad develops on the right of the midline, with the gut bilaterally apposed on the left. However, we found that in males of the laboratory N2 strain and Hawaiian (“Hw”) wild isolate, the gut/gonad asymmetry is frequently reversed in a temperature-dependent manner, independent of normal embryonic chirality. We also observed sporadic errors in gonad migration occurring naturally during early larval stages of these and other wild strains; however, the incidence of such errors does not correlate with the frequency of L/R gut/gonad reversals in these strains. Analysis of N2/Hw hybrids and recombinant inbred advanced intercross lines (RIAILs) indicate that the L/R organ reversals are likely to result from recessively acting variations in multiple genes. Thus, unlike the highly reproducible L/R asymmetries of most structures in hermaphrodites, the L/R asymmetry of the male C. elegans body plan is less rigidly determined and subject to natural variation that is influenced by a multiplicity of genes.

Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality

“…Coordination among these axes is critical as any misinterpretation could lead to severe birth defects 4, 22, 33 . On a 2D substrate, cell migration direction is directly linked to the back-front (BF) polarity through the polarized shape that migrating cells take on 14, 21, 30, 41, 44, 49 .…”

Heterotaxy inCaenorhabditis: widespread natural variation in left–right arrangement of the major organs

“…We previously reported that the L/R gut/gonad asymmetry in N2 males raised at 25°C is frequently (more than 5%) reversed [40], with the fully developed gut occupying the position on the right normally taken by the gonad (figure 1). These reversals do not appear to reflect a complete inversion of L/R anatomy, as a marker of the right-specific ASER neuron is expressed in its normal position on the right [34].…”

“…In addition, viable sinistral animals can arise as a result of mutations in gpa-16 [17], which encodes a small rho-GTPase required for normal spindle placement, and in the actin cytoskeleton [32], leading to reversal of AB spindle skewing. However, several studies of a large number (more than 15 000) of animals [17,35,40,42] reared at 208C indicated that such L/R left-right reversals in the arrangement of the major organs in the laboratory N2 isolate do not occur under normal conditions, suggesting that evolutionary constraints have led C. elegans to adopt a virtually invariant dextral body plan. We previously reported that the L/R gut/gonad asymmetry in N2 males raised at 258C is frequently (more than 5%) reversed [40], with the fully developed gut occupying the position on the right normally taken by the gonad (figure 1).…”

“…However, several studies of a large number (more than 15 000) of animals [17,35,40,42] reared at 208C indicated that such L/R left-right reversals in the arrangement of the major organs in the laboratory N2 isolate do not occur under normal conditions, suggesting that evolutionary constraints have led C. elegans to adopt a virtually invariant dextral body plan. We previously reported that the L/R gut/gonad asymmetry in N2 males raised at 258C is frequently (more than 5%) reversed [40], with the fully developed gut occupying the position on the right normally taken by the gonad (figure 1). These reversals do not appear to reflect a complete inversion of L/R anatomy, as a marker of the right-specific ASER neuron is expressed in its normal position on the right [34].…”

“…However, L/R differences between some cell types that are made stochastically [39], and the L/R motor handedness bias of male mating [24], are independent of this embryonic chirality. Further, we found that the stereotyped L/R arrangement of the intestine and gonad of males in the laboratory isolate is frequently reversed at elevated temperature, independent of the overall anatomical handedness of the animal (electronic supplementary material, table S1 and figure S2; [40]), suggesting that the symmetry-breaking mechanism leading to the bilateral orientation of these organs is at least partially separable from the event that creates chirality of the embryo.…”