The apparent left/right (L/R) symmetry of the early C. elegans embryo is broken between the 4- and 6-cell stages of cleavage when the L/R-oriented spindles in the anterior blastomeres ABa and ABp skew in a clockwise direction (viewed dorsally). The resulting cleavage produces an asymmetric 6-cell embryo and establishes the handedness of all subsequent L/R asymmetries in development (Wood, Nature 349:536, 1991). Handedness choice is essentially invariant, so that animals with reversed situs are not seen in wild-type populations (<10 -4 ). The ts maternal-effect mutation
spn-1(
it143) causes misorientation of spindles in the second and third cleavages at 25deg, affecting ABa and ABp most severely. The result is 70% embryonic lethality, with 40% of the surviving progeny showing reversed situs (Bergmann & Wood, Int. C. elegans Meeting Abstr. 187, 1999). We mapped
spn-1 to a region of LGI including the predicted G a protein gene
gpa-16 (Jansen et al., Nature Genet 21:414-419, 1999). The
spn-1 mutation failed to complement
gpa-16(
pk481) , a deletion mutation (kindly provided by G. Jansen), which in a
gpa-16(
pk481);
dpy-20(
e1282) strain also causes incompletely penetrant maternal-effect embryonic lethality. Sequencing of
gpa-16 cDNA from
spn-1(
it43) revealed a single base change, causing the substitution G202D in a conserved region of the predicted G a protein product. Together with the recent demonstration that this protein is involved in control of a G b g complex regulating centrosomal migration and hence spindle orientation in early embryos (Gotta & Ahringer, Nature Cell Biol 3:297-300, 2001), our findings begin to explain how the
spn-1(
it143) mutation affects handedness choice and suggest that the initial symmetry-breaking event may act through heterotrimeric G protein signaling.