DNA replication defects delay cell division and disrupt cell polarity in early Caenorhabditis elegans embryos

In early Caenorhabditis elegans embryos, asymmetric cell divisions produce descendants with asynchronous cell cycle times. To investigate the relation ship between cell cycle regulation and pattern formation, we have identifie d a collection of embryonic-lethal mutants in which cell divisions are dela yed and cell fate patterns are abnormal. In div (for division delayed) muta nt embryos, embryonic cell divisions are delayed but remain asynchronous. S ome div mutants produce well-differentiated cell types, but they frequently lack the endodermal and mesodermal cell fates normally specified by a tran scriptional activator called SKN-1. We show that mislocalization of PIE-1, a negative regulator of SKN-1, prevents the specification of endoderm and m esoderm in div-1 mutant embryos. In addition to defects in the normally asy mmetric distribution of PIE-1, div mutants also exhibit other losses of asy mmetry during early embryonic cleavages. The daughters of normally asymmetr ic divisions are nearly equal in size, and cytoplasmic P-granules are not p roperly localized to germline precursors in div mutant embryos. Thus the pr oper timing of cell division appears to be important for multiple aspects o f asymmetric cell division. One div gene, div-1, encodes the B subunit of t he DNA polymerase alpha -primase complex. Reducing the function of other DN A replication genes also results in a delayed division phenotype and embryo nic lethality. Thus the other div genes we have identified are likely to en code additional components of the DNA replication machinery in C. elegans. (C) 2000 Academic Press.