REGULATION OF MOUSE PREIMPLANTATION DEVELOPMENT - INHIBITORY EFFECT OF THE CALMODULIN ANTAGONIST W-7 ON THE 1ST CLEAVAGE

The calmodulin antagonist W‐7 inhibits cleavage of 1‐cell mouse embryos in a concentration‐dependent manner. This inhibition is likely to be specific for a calmodulin‐mediated process, since the less active congener W‐5 does not inhibit cleavage when used at concentrations of W‐7 that do. Concentrations of W‐7 that inhibit cleavage and do not inhibit either the uptake or incorporation of [35S]methionine do inhibit [3H]thymidine incorporation; similar concentrations of W‐5 do not inhibit [3H]thymidine incorporation. Consistent with W‐7′s ability to inhibit cleavage by inhibiting DNA synthesis is that addition of W‐7 at later times that correspond with exit from S phase results in cleavage to the 2‐cell stage. Although W‐7 does inhibit cleavage of 1‐cell embryos, it does not inhibit transcriptional activation, which occurs in the 2‐cell embryo and is characterized by the synthesis of a group of proteins of Mr = 70,000. Results of these experiments suggest a role for calmodulin in the first cell cycle of the mouse embryo and provide another example in which zygotic gene activation is not dependent on progression through the first cell cycle. Copyright © 1990 Wiley‐Liss, Inc.