Lithium changes the ectodermal fate of individual frog blastomeres because it causes ectopic neural plate formation

Amphibian blastulae that are treated with lithium (Li) develop into embryos that consist almost exclusively of head structures. This dramatic change in embryogenesis may occur either because Li selectively kills trunk progenitors or because Li causes trunk progenitors to become head progenitors. To distinguish between these possibilities, we compared the fates of individual frog blastomeres between Li-treated embryos and normal embryos using lineage tracers. The results demonstrate that Li causes ventral midline cells, which normally populate large amounts of trunk, to produce many head structures, including the brain. Examination of fluorescently labeled clones in living Li-treated gastrulae shows that: (1) the ectodermal members of the clones migrate normally, and chordamesodermal involution begins normally; (2) the chordamesoderm's later involution is altered such that it is confined to the vegetal hemisphere; (3) accordingly, the neural plate forms in the vegetal hemisphere, circumscribing the blastopore, which normally gives rise to the cloaca; and (4) the ectodermal progeny of the ventral midline blastomeres that are near the blastopore populate the brain because they are induced by the stalled chordamesoderm to form part of the ectopic neural plate. These results demonstrate that Li, administered during a short developmental window at early cleavage stages, ultimately alters ectodermal fate because it changes the pattern of chordamesodermal involution during gastrulation, which in turn changes the site of neural plate formation.