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A quantitative, high-resolution, two-dimensional gel protein database has been constructed for the mouse embryo. This database has been used to obtain a detailed accounting of the amount and relative timing of changes in protein synthesis that occur during the 1-, 2-, and 4-cell stages along with a description of the most prevalent developmentally regulated patterns of synthesis. We find that during these early stages of development the pattern of proteins synthesized changes to a much greater extent than previously appreciated. During the 1- and 2-cell stages, the majority (60 % and 85 %, respectively) of the analyzed proteins exhibit twofold or greater changes in their rates of synthesis. The periods of greatest change are the late 1-cell and mid 2-cell stages, during which an extensive remodelling of protein synthetic pattern occurs that is largely complete by 15 h following the first cleavage. Once this reprogramming is complete, very little change is observed during the late 2-cell and 4-cell stages. Cluster analysis of individual protein synthesis patterns reveals a limited number of coordinately regulated protein sets that are responsible for most of the changes observed during the and 2-cell stages. During the 2-cell stage, one third of the proteins increase by an average of fivefold, another third decrease by an average of sevenfold, and 10% undergo transient changes in rates of synthesis. These patterns reflect the switch from zygotic to maternal mRNA utilization following transcriptional activation. Significantly, a set of proteins exhibiting relatively constant rates of synthesis is not observed during the 2-cell stage, indicating that the rate of synthesis of almost every detectable protein changes significantly during this period. Overall, our data indicate that the transition from maternal to embryonic control of development results in an abrupt and extensive reprogramming of the early embryo with respect to the pattern of proteins synthesized.

Moutier1discovered, in a mouse from a noninbred Swiss/Orleans laboratory stock, a spontaneous dominant mutation which mapped to the T locus, and which was named Tor1. Genetic analyses indicated that Tor1was not a simple mutation at one locus, but rather a deletion over a 3-centimorgan region of chromosome 17 that included both T and quaking (qk)2,3. Further experiments reported by Erickson et al.3, and a more comprehensive study by Hammerberg4, have demonstrated that Tor1is associated with recessive genetic properties affecting sperm function, characteristic of the proximal region of complete t haplotypes. These results were interpreted as evidence for the location of proximal t haplotype ‘sperm factors’ within the region deleted by Tor1. We now provide conclusive biochemical and genetic evidence that the ‘Tor1haplotype’ is inseparably associated with a chromosomal region derived from a naturally occurring mouse t haplotype. Hence, it is likely that the t haplotype properties of Tor1are a consequence not of the deletion itself, but of closely linked mutant t haplotype genes.