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S15-05 Cellular antennae: The role of primary cilia in human disease
MECHANISMS OF DEVELOPMENT
1 2 6 ( 2 0 0 9 ) S 1 6 –S 1 7
S17
response of cancer cells to external cues and disrupting cell and
single animals and populations of worms. It will be very useful
tissue architecture.
for the molecular dissection of sensory perception in CSN and for the analysis of developmental aspects of ciliogenesis.
doi:10.1016/j.mod.2009.06.986
S15-04 Worms with only a single cilium Sˇ.. per animal Peter Swoboda So¨derto¨rn University College, Huddinge, Sweden It is crucial to be able to correctly detect and interpret environmental signals. Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm C. elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSN) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development, function and behavior. We have generated a genetic rescue system that allows invivo analyses of isolated CSN at both cellular and systemic levels. We used the RFX transcription factor DAF-19, a key regulator of ciliogenesis. Mutations in daf-19 result in the complete absence of all sensory cilia and therefore of external sensory input. In daf-19 mutants we used cell-specific rescue of DAF-19 function in only selected neurons, thereby generating animals with single, fully functional CSN. Otherwise and elsewhere these animals are completely devoid of any environmental input through cilia. We demonstrated the rescue of fully functional, single cilia using visual inspection with fluorescent markers, sensory behavioral assays, and optical activity (calcium) imaging. Our technique can thus cell-autonomously and cell-specifically restore the function of single sensory neurons and their ability to respond to sensory input. It can easily be adapted to any CSN, and thus constitutes an excellent tool to study sensory behaviors, both in
doi:10.1016/j.mod.2009.06.987
S15-05 Cellular antennae: The role of primary cilia in human disease Philip Beales University College London, London, United Kingdom Studies during the last eight years indicate that primary cilia are far from redundant and more likely serve a broad sensory purpose transducing extracellular information to the cell interior. More recently, studies have indicated additional but central roles for cilia in several signal transduction pathways including the Wnt noncanonical (or Planar Cell Polarity pathway (PCP)), the Sonic Hedgehog (SHH) pathway and for regulation of intracellular Ca2+ concentration. Perturbation of ciliary proteins can give rise to a broad but consistent range of phenotypes in mammals including retinal degeneration, anosmia, renal, hepatic and pancreatic cyst formation, post-axial polydactyly and situs inversus. It was these observations that led our group to propose that ciliary dysfunction underlies the Bardet–Biedl syndrome (BBS) and other inherited syndromes. The further study of the mechanistic basis for BBS and allied disorders (collectively termed the’’ciliopathies’’) has great potential to further our understanding of cilia biology in general and more specifically reveal their role in developmental disorders and disease. I will present evidence for the role of primary cilia related proteins in signalling, cell migration and development and the effect of their perturbation in human disease. doi:10.1016/j.mod.2009.06.988
1 2 6 ( 2 0 0 9 ) S 1 6 –S 1 7
S17
response of cancer cells to external cues and disrupting cell and
single animals and populations of worms. It will be very useful
tissue architecture.
for the molecular dissection of sensory perception in CSN and for the analysis of developmental aspects of ciliogenesis.
doi:10.1016/j.mod.2009.06.986
S15-04 Worms with only a single cilium Sˇ.. per animal Peter Swoboda So¨derto¨rn University College, Huddinge, Sweden It is crucial to be able to correctly detect and interpret environmental signals. Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm C. elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSN) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development, function and behavior. We have generated a genetic rescue system that allows invivo analyses of isolated CSN at both cellular and systemic levels. We used the RFX transcription factor DAF-19, a key regulator of ciliogenesis. Mutations in daf-19 result in the complete absence of all sensory cilia and therefore of external sensory input. In daf-19 mutants we used cell-specific rescue of DAF-19 function in only selected neurons, thereby generating animals with single, fully functional CSN. Otherwise and elsewhere these animals are completely devoid of any environmental input through cilia. We demonstrated the rescue of fully functional, single cilia using visual inspection with fluorescent markers, sensory behavioral assays, and optical activity (calcium) imaging. Our technique can thus cell-autonomously and cell-specifically restore the function of single sensory neurons and their ability to respond to sensory input. It can easily be adapted to any CSN, and thus constitutes an excellent tool to study sensory behaviors, both in
doi:10.1016/j.mod.2009.06.987
S15-05 Cellular antennae: The role of primary cilia in human disease Philip Beales University College London, London, United Kingdom Studies during the last eight years indicate that primary cilia are far from redundant and more likely serve a broad sensory purpose transducing extracellular information to the cell interior. More recently, studies have indicated additional but central roles for cilia in several signal transduction pathways including the Wnt noncanonical (or Planar Cell Polarity pathway (PCP)), the Sonic Hedgehog (SHH) pathway and for regulation of intracellular Ca2+ concentration. Perturbation of ciliary proteins can give rise to a broad but consistent range of phenotypes in mammals including retinal degeneration, anosmia, renal, hepatic and pancreatic cyst formation, post-axial polydactyly and situs inversus. It was these observations that led our group to propose that ciliary dysfunction underlies the Bardet–Biedl syndrome (BBS) and other inherited syndromes. The further study of the mechanistic basis for BBS and allied disorders (collectively termed the’’ciliopathies’’) has great potential to further our understanding of cilia biology in general and more specifically reveal their role in developmental disorders and disease. I will present evidence for the role of primary cilia related proteins in signalling, cell migration and development and the effect of their perturbation in human disease. doi:10.1016/j.mod.2009.06.988