The fragile centrioles (fract) gene is required for the maintenance of centriole integrity during Drosophila male meiosis.
Centrioles are highly conserved structures found at the core of the centrosome, the primary microtubule-organizing center in animal cells. Proper centriole duplication prevents centrosome amplification, which causes genomic instability and is a characteristic of many types of cancer. Centrioles are also essential for the formation of cilia and flagella that play critical roles in physiology, development and disease. We are studying centriole biology using Drosophila as model system.
We have isolated and characterized a mutation in a Drosophila melanogaster gene we name
fragile centrioles (fract); this mutation disrupts male meiosis and causes male sterility.
Immunostaining with antibodies against centriolar components such as DSpd2 and Asl showed
that premeiotic spermatocytes of fract mutants display 2 centrioles at each cell pole. However,
the cell poles of meiotic ana-telophases I of fract mutants often exhibit two centrioles of different length or a single centriole. As a result, a number of secondary spermatocytes
assemble bipolar monastral spindles that are unable to mediate proper chromosome
segregation. fract encodes a 322 aa protein that contains WD repeats; this protein is expressed
only in testes, suggesting that fract is specifically required for meiotic centriole stability. The
EMS-induced fract1 mutant allele we characterized carries a stop codon that truncates the Fract
protein into a 295 aa polypeptide. A polyclonal antibody raised against Fract decorates the distal
ends of male meiotic centrioles. This specific staining pattern is lost in fract mutants, where the
antibody decorates the entire centriole, suggesting that the C-terminal region of Fract is crucial
for its correct localization. A newly developed centriole stability assay indicated that the centrioles of fract mutants are more sensitive to colchicine-induced depolymerization than their wild type counterparts. Collectively our results strongly suggest that fract does not play an essential role
in centriole assembly but it is instead required for the maintenance of centriole integrity during
male meiosis, a function never described in other organisms.