Drosophila melanogaster as a model to study ciliogenesis

• Main Author: Pratt, Metta
• Other Authors: Raff, Jordan
• Published: University of Oxford 2016
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730392

Cilia are microtubule-based extensions of the cell membrane that extend from a mature centriole. Primary (non-motile) cilia are present on most human cells and have important roles in signalling pathways. At the base of the cilium is a selective barrier known as the transition zone (TZ). Defects in the TZ are associated with human congenital diseases such as Meckel-Gruber syndrome (MKS) and Nephronophthisis (NPHP). The TZ is formed by three protein complexes, the MKS, NPHP and Cep290 modules, although the fruit fly Drosophila melanogaster appears to lack the core components of the NPHP module. Results presented in this thesis shows that MKS proteins are spatially separated from Cep290 at the TZ in Drosophila spermatocyte cilia. The TZ of the spermatocyte cilia is perturbed in flies mutant for MKS1 (MKS1Δ1) and fails to recruit key TZ proteins, although Cep290 and Chibby are recruited normally. Male fertility, however, is unaffected. Similarly, while there are substantial abnormalities in microtubule and membrane organisation in developing MKS1Δ1 mutant cilia, defects in mature MKS1Δ1 mutant cilia are limited to subtle changes in IFT and a membrane surrounded volume within the cilium. The function of sensory neurons is not negatively affected by the MKS1Δ1 mutation. Evidently, given enough developmental time, ciliary defects can be largely rescued in flies and the localisation of MKS module proteins to the cilia or flagella is not essential for viability or fertility in Drosophila.