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 P(11/12)L and P(1 1/12)R are symmetric left-right homologs at hatching, migrate subsequently in opposite anteroposterior directions during the first larval stage, and a dopt two different fates, thus breaking the symmetry between them. Our resu lts show that, unlike most other cell fate decisions in C. elegans, the ori entation of P(11/12)L/R migration is highly biased, but not fixed. The hand edness of their migration is linked to whole body handedness and is randomi zed in lin-12/Notch mutants and by ablation of the Y cell. Migration handed ness 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. St ernberg, 1998, Development 125, 2337-2347). We further show that several ch anges in P(11/12)L/R asymmetry have occurred during nematode evolution: los s of asymmetry or reversals in orientation of migration. Strikingly, for mo st species studied, handedness of migration is highly biased but not fixed. Thus, whereas the final cell fate pattern of P11/12 is invariant, the deve lopmental route leading to it is subject both to developmental indeterminac y and to evolutionary variations. (C) 2001 Academic Press.