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Kawafi, A.

Publications and source records attributed to Kawafi, A..

2 recordsLinked to original sources

Tuning Collective Behaviour in Zebrafish with Genetic Modification

Zebrafish collective behaviour is widely used to assess their physical and mental state, serving as a valuable tool to assess the impact of ageing, disease genetics, and the effect of drugs. The essence of these macroscopic phenomena can be represented by active matter models, where the individuals are abstracted as interactive self-propelling agents. The behaviour of these agents depends on a set of parameters in a manner reminiscent of those between the constituents of physical systems. In a few cases, the system may be controlled at the level of the individual constituents such as the interactions between colloidal particles, or the enzymatic behaviour of de novo proteins. Usually, however, while the collective behaviour may be influenced by environmental factors, it typically cannot be changed at will. Here, we challenge this scenario in a biological context by genetically modifying zebrafish. We thus demonstrate the potential of genetic modification in the context of controlling the collective behaviour of biological active matter systems at the level of the constituents, rather than externally. In particular, we probe the effect of the lack of col11a2 gene in zebrafish, which causes the early onset of osteoarthritis. The resulting col11a2 -/- zebrafish exhibited compromised vertebral column properties, bent their body less while swimming, and took longer to change their orientations. Surprisingly, a group of 25 mutant fish exhibited more orderly collective motion than the wildtype. We show that the collective behaviour of wildtype and col11a2 -/- zebrafish are captured with a simple active matter model, in which the mutant fish are modelled by self-propelling agents with a higher orientational noise on average. In this way, we demonstrate the possibility of tuning a biological system, changing the state space it occupies when interpreted with a simple active matter model.

animal behavior and cognition↗

NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss

Hearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of 13cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C>G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3-/- did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3-/-, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3-/- and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.

genetics↗