| Early embryonic development requires the proper coordination of many diverse processes, including establishment of the embryonic axes, onset of embryonic transcription, and cell cycle progression. A favorite approach of developmental biologists to study these processes has been the isolation of genetic mutants defective in these processes, and then to clone and characterize the defective genes. Here we describe genetic screens for embryonic lethal mutants in C. elegans designed to identify mutants defective in many of these processes. Many of the mutants isolated represent new alleles of the previously identified par class of genes, which play a central role in the generation of embryonic polarity. A second class of mutants has a defect in cell cycle progression such that they arrest at the metaphase to anaphase transition of oocyte meiosis I. Interestingly, embryonic polarity is also affected in these mutants. We have used these mutants to show that the cue to which the PAR proteins respond to establish embryonic polarity derives from microtubules. In wild type embryos this microtubule cue comes from the sperm asters, but in these mutant embryos the microtubule cue is provided by the meiotic spindle, which results in the observed polarity defects. A third class of mutants identified has defects in embryonic transcription. Interestingly, one of these mutants additionally shows defects in cell cycle progression. We show that this mutant is an allele of the C. elegans cdk7 homologue. Cdk7 has long been proposed to be the kinase responsible for the activation of other cyclin-dependent kinases, however proof this role in vivo has been elusive, due to the essential role of cdk7 in transcriptional activation. We show that the C. elegans cdk7 mutant has independent transcriptional and cell cycle defects, supporting its proposed dual function. While the genes described in the present study have diverse roles, they each underscore the interconnectedness of the processes that they affect in the early embryo. In the final chapter, directions for further study that derive from this work are discussed. |
