Development and evolution of a variable left-right asymmetry in nematodes: the handedness of P11/P12 migration.

In Caenorhabditis elegans, two lateral blast cells called P11/12L and P11/12R are symmetric left-right homologs at hatching, migrate subsequently in opposite anteroposterior directions during the first larval stage, and adopt two different fates, thus breaking the symmetry between them. Our results show that, unlike most other cell fate decisions in C. elegans, the orientation of P11/12L/R migration is highly biased, but not fixed. The handedness of their migration is linked to whole body handedness and is randomized in lin-12/Notch mutants and by ablation of the Y cell. Migration handedness is independent of P11 and P12 fate determination, previously shown to require the LIN-44/Wnt and the LIN-3/EGF pathways (L. I. Jiang and P. W. Sternberg, 1998, Development 125, 2337-2347). We further show that several changes in P11/12L/R asymmetry have occurred during nematode evolution: loss of asymmetry or reversals in orientation of migration. Strikingly, for most species studied, handedness of migration is highly biased but not fixed. Thus, whereas the final cell fate pattern of P11/12 is invariant, the developmental route leading to it is subject both to developmental indeterminacy and to evolutionary variations. Copyright 2001 Academic Press.