Cilia are microtubule-based organelles that project into the extracellular space and have various functions including transducing sensory information, regulating developmental signalling pathways, and generating directed fluid flow, making them important regulators of vertebrate development and homeostasis. Despite their importance, there are many aspects of cilia formation and function that remain poorly understood. The planar cell polarity (PCP) pathway is a branch of Wnt signalling that provides positional information to cells and is required for polarized morphogenic cell movements. Previous studies of PCP effector proteins suggested that PCP signalling was required for cilia formation. However, these proteins are not specific to the PCP pathway and are shared with other branches of Wnt signalling. To determine the role of a core and specific PCP regulator on ciliogenesis, I examined maternal-zygotic (MZ) vangl2 zebrafish mutants using an in vivo marker of cilia, Arl13b-GFP. Analysis of MZvangl2 mutants revealed that PCP is not required for cilia formation but is required for the posterior tilting and posterior positioning of motile cilia, essential for directed fluid flow. A parallel branch of studies suggested that cilia are actually required to regulate PCP signalling because defects in PCP-mediated morphogenic movements were observed with the knockdown of certain proteins that localize at or near cilia or basal bodies. To determine whether cilia were required to establish PCP, I generated MZ-intraflagellar transport-88 (IFT88) mutants, where ciliogenesis is completely abolished. Analysis of MZift88 mutants revealed that cilia are not directly required for PCP-mediated morphogenic movements. However, I observed that MZift88 mutants had defects in oriented cell divisions (OCD) occurring during gastrulation. Remarkably, these divisions occur prior to cilia formation, suggesting a cilia-independent role for IFT proteins in cell divisions, which may have important consequences on the interpretation of the role of cilia in disease.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43469 |
| Date | 07 January 2014 |
| Creators | Borovina, Antonija |
| Contributors | Ciruna, Brian Garrett |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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