Worm Breeder's Gazette 14(4): 26 (October 1, 1996)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Lithium arrests embryonic development of C. elegans

Yo Tabuse

NEC Fundamental Research Laboratories, Miyukigaoka 34, Tsukuba, Ibaraki 305, Japan

     Lithium (Li) has long been known to have teratogenic
effects on the development of many organisms, including sea
urchin, Xenopus and Dictyostelium. In Li-treated Xenopus
embryos, ventral blastmeres are respecified to develop into
dorsal structures, leading to dorsalized embryos lacking
ventral mesodermal tissues. In Dictyostelium, Li alters the
fate of prespore cells to become prestalk cells instead.
Besides teratogenic effects, Li is also known to bea most
effective  treatment of manic-depressive illness.
     Although several models have been proposed to explain
Li action, the molecular mechansm remains unclear. The most
widely accepted model is the inositol depletion hypothesis,
in which  Li is thought to affect inositol phosphate
turnover by inhibiting inositol monophosphatase, thus
resulting in the depletion of endogenous inositol.
     To understand the mechanism of Li action, I first
examined the effect of Li on C. elegans embryogenesis. I
inoculated N2 animals at the late L4 stage onto NG plates
containing 20 mM LiCl, incubated them at 20 C and observed
the laid embryos. The number of eggs produced by treated
animals was reduced to about half of the untreated control.
Although cell division seemed to proceed, no embryos hatched
on Li plates. Treated-embryos developed to produce gut
granules, but did not execute normal morphogenesis at later
embryonic stages.
     To identify genes involved in the action of Li, I have
begun to screen for Li-resistant mutants, which propagated
on Li-containing medium. So far, I obtained one mutant. The
mutation was tentatively assigned to chromosome V.
Preliminary genetic analysis showed that the mutation showed
maternal effect. On Li plates, the hatching rate of mutant
eggs cross-fertilized by wild-type males was essentially the
same as that for self-fertilized mutant eggs. On the
contrary, no wild-type eggs cross-fertilized by mutant males
hatched on Li-containing plates. I am now trying to isolate
other mutants and also to identify early defects of
embryogenesis caused by lithium treatment.
     I would like to thank J. Miwa for encouragement and