Daniel Vasiliauskas Team
Neurogenetics of Drosophila
How do genetic programs differ between individuals to create unique brains? And, how do different neuron types in a brain establish and then maintain their functional differences? We address these questions by investigating the molecular mechanisms and genetic basis of specification, maintenance and natural variation of different colour sensitivities in fly photoreceptor neurons.
Our team is interested in two broad questions :
• How does the nervous system vary in natural populations ?
• How do neurons maintain their functional identities ?
We use powerful genetic approaches of the Drosophila melanogaster (fruit fly) model organism to address these questions in photoreceptor neurons of the adult retina. Specifically, we focus on the R8 photoreceptor type which can express one of two Rhodopsins, Rh5 or Rh6. Thus, we are investigating the natural variation of the Rh5/Rh6 expression pattern, and also how this pattern is maintained, once it has been established during development.
Natural variation of Drosophila Rh expression
Most recent effort has been focused on the first of the above two questions. How small changes in our genomes cause dramatic changes in sensation, neuronal processing and behaviour is poorly understood. Though genome-wide association studies have identified numerous potential genetic variants causing neurological disease or normal phenotypes, further studies to understand how these genetic changes affect phenotypes at the molecular level are often not feasible. We decided to apply powerful tools available in model organisms to study the natural variation of neurological development and behaviour, to identify the underlying genetic causes and to investigate the affected molecular mechanisms. Since the developmental program of the fly retina is one of the best understood for a sensory system, we focused on how natural variation affects colour photoreceptor cell fate specification and maintenance, and the behavioural changes that depend on light perception.
In humans, there is a surprising level of natural variation affecting the visual system. The ratios of different colour photoreceptors differ vastly throughout the population. Colorblindness caused by mutations in the opsin genes are relatively common, affecting about 10% of male population. And, a vast number of rare mutations affecting a long list of genes cause devastating retinal degeneration pathologies. Our work so far suggests that similar situation exists in natural Drosophila populations : the ratios of photoreceptor types vary extensively, mutations in Rhodopsin genes occur with moderate frequency, and many of the retina developmental genes can carry rare strong-impact mutations. We have established a solid basis for pursuing these variants in Drosophila with two goals in mind : learning more about eye development, and learning more about the architecture of natural variation in the visual system.
> Alejevski, F., Saint-Charles, A., Michard-Vanhée, C., Martin, B., Galant, S., Vasiliauskas, D., and Rouyer, F. (2019) The HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles. Nature Communications 10, Article number : 252, DOI:10.1038/s41467-018-08116-7
> Anderson, C., Reiss, I., Zhou, C., Cho, A., Siddiqi, H., Morman, B., Aviles, C.M., Deford, P., Bergland, A., Roberts, E., Taylor, J., Vasiliauskas, D., and Johnston, R.J., Jr. (2017) Natural variation in stochastic photoreceptor specification and color preference in Drosophila. eLife, 6, e29593.58.
> Rister, J., Desplan, C., and Vasiliauskas, D. (2013) Establishing and maintaining gene expression patterns : insights from sensory receptor patterning. Development 140, 493-503.
> Hsiao, H.Y., Johnston Jr., R.J., Jukam, D., Vasiliauskas, D., Desplan, and C., Rister, J. (2012) Dissection and Immunohistochemistry of Larval, Pupal and Adult Drosophila Retinas. J. Vis. Exp. (69), e4347, doi:10.3791/4347.
> Vasiliauskas, D., Mazzoni, E.O., Sprecher, S.G., Brodetskiy, K., Johnston, R.J.Jr., Lidder, P., Vogt, N., Celik, A., and Desplan, C. (2011) Feedback from Rhodopsin controls rhodopsin exclusion in Drosophila photoreceptors. Nature, 479, 108-12.