Infoscience

Thesis

Mechanisms of differential centriole inheritance in C. elegans

Centrosomes are the principal microtubule organizing center (MTOC) of animal cells and comprise a pair of centrioles surrounded by pericentriolar material (PCM). Centriole number must be carefully regulated to ensure bipolar spindle formation and thus faithful chromosome segregation. In the germ line of most metazoan species, centrioles are maintained during spermatogenesis, but eliminated during oogenesis. Such differential behavior ensures that the appropriate number of centrioles is present in the newly fertilized zygote. In this doctoral thesis work, I describe our investigation of centriole elimination during oogenesis in C. elegans and I characterize sas-1, a factor important for maintaining centriole integrity, especially during spermatogenesis, to ensure that two centrioles are present in the zygote. Despite being a fundamental feature of sexual reproduction in metazoans, themechanisms governing centriole elimination during oogenesis are poorly understood. We investigate this question using antibodies directed against centriolar components and serial-section electron microscopy and we establish that centrioles are eliminated during the diplotene stage of the meiotic cell cycle. Moreover, we show that centriole elimination is compromised upon depletion of the helicase CGH-1. We also find that somatic cellsmake a minor contribution to this process, and demonstrate that the germcell karyotype is important for timely centriole elimination. These findings set the stage for a mechanistic dissection of centriole elimination in ametazoan organism. How centriole integrity is ensured after organelle assembly is poorly understood, including in sperm cells, where such integrity is particularly critical. In a genetic screen in C. elegans, sas-1 was identified as a locus important for the maintenance of centrioles in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is absent. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles once they are assembled. Futhermore, we demonstrate that SAS-1 can bind and stabilize microtubules when expressed in human cells. We also identify C2CD3, a protein required for proper centriole formation, as a putative mammalian SAS-1 homolog. Together, we uncover an important component required for maintaining centrioles in sperm cells to ensure that two centrioles are present after fertilization and thus guarantee the continuity of the species.

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