The 4-cell stage blastomere EMS divides asymmetrically along the anterior-posterior (A/P) axis of the embryo and produces two daughters with distinct cell fates. The fates of the EMS daughters and the A/P orientation of the EMS division axis are specified by signaling from the neighboring blastomere P2. P2/EMS signaling involves at least two partially redundant pathways, a WNT signaling pathway and a phoshpotyrosine signaling pathway (see abstract by Bei et al.,). A complex composed of WRM-1/ß-catenin and the SER/THR kinase LIT-1 controls cell fate downstream of P2/EMS signaling. However, neither of these factors are required for the A/P oreintation of the EMS division. While mutations in some components of WNT signaling have been shown in blastomere isolation experiments to have defects in EMS spindle orientation, intact embryos do not reveal this role. Here we describe a recessive maternal effect mutation,
ne236 , that completely converts the normally A/P orientation of the EMS spindle to left/right in intact embryos. Despite the change in EMS, cell divisions previous to the six cell stage are normal, and the germ line cells continue divide properly and to segregate P granules properly until the end of embryogenesis. All embryos from homozygous
ne236 mothers arrest development without body enclosure and with cell fate changes including changes consistent with defects in P2/EMS signaling. Surprisingly, we found that
ne236 is an allele of
cdk-1 (previously known as
ncc-1 ) , the C. elegans homolog of the yeast cyclin dependent kinases CDC-2 and CDC28. Null alleles of
cdk-1 exhibit mid-larval mitotic arrest and lethality that appears to coincide with exhaustion of maternally provided CDK-1. Depletion of maternal CDK-1 by RNAi causes a one cell meiotic arrest. In contrast,
cdk-1(
ne236) homozygotes have no obvious zygotic phenotype, and produce mutant embryos that have normal cell divisions and the normal numbers of well differentiated cells. Furthermore
ne236 in trans to a deficiency appears identical to
ne236 homozygotes suggesting that the
ne236 allele is not significantly impaired for meiotic or mitotic functions of
cdk-1 . Thus
ne236 appears to cause a recessive loss of one specific function of CDK-1 leaving most or perhaps all of its other cell cycle regulatory activities intact. Interestingly, genetic tests suggest that the spindle orientation defect of
cdk-1(
ne236) is suppressible by removing certain P2/EMS signaling components, including
wrm-1 , the ß-catenin homolog. Since loss of
wrm-1 has a strong EMS cell fate defect but gives the wild type A/P spindle orientation, this finding suggests a model for division axis control in EMS. The default spindle orientation for EMS may in fact be A/P. WRM-1 in concert with other factors may mask this default polarity cue when, for example, the function of CDK-1 is altered, or, as further experiments have revealed, when other components of the P2 to EMS signal are perturbed (see abstract by Bei et al.,). We therefore propose that CDK-1 may directly or indirectly regulate target(s) at a key step in the cell cycle to unmask an asymmetry site that directs EMS spindle orientation.