INJECTION OF MYOINOSITOL REVERSES THE EFFECTS OF LITHIUM ON SEA-URCHIN BLASTOMERES

Lithium is known to cause sea urchin blastomeres destined to give rise to epithelium rather than to differentiate into gut or skeleton. Whil e it has been proposed that lithium alters development by interfering with the inositol-tris phosphate-protein kinase C (IP3-PKC) signaling pathway, the mechanism of action of lithium-in sea urchins has remaine d elusive. Here we describe experiments that examine the hypothesis th at lithium exerts its effect on sea urchin embryos via the IP3-PKC pat hway. We make use of methods developed to isolate epithelial precursor cells from the animal hemisphere of cleavage 16-cell stage embryos. P airs of cells were isolated and one of each pair was injected with eit her myo-inositol or its inactive isomer, epi-inositol. Rhodamine dextr an was co-injected as a lineage tracer to follow the fate of injected cells. We demonstrate that injected myo-inositol, but not epi-inositol , can reverse the effects of lithium on sea urchin blastomeres. This i s direct evidence that lithium affects the IP3-PKC pathway in sea urch ins, and that this pathway plays an important role in cell fate determ ination.