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Neurogenetics of Drosophila

Group leader : Daniel Vasiliauskas

Our team is interested in two broad questions :
- How the nervous system varies in natural populations ?
- And, how neurons maintain their functional identities ?
We use powerful genetic approaches of Drosophila melanogaster (fruit fly) model organism to address these questions in photoreceptor neurons of the adult retina. Specifically, we focus on Rh8 photoreceptor type which can express one of two Rhodopsins, Rh5 or Rh6. Thus, we are investigating the natural variation of Rh5/Rh6 expression pattern, and also how this pattern is maintained, once it has been established during development.

Most of the effort in the recent period was focussed on the first of the above two questions. Our goal was to develop a strategy for identification of genetic variants that underlie the phenotypic natural variants encountered in the wild.

  • We completed a screen (started before joining the Neuro-PSI in 2016) of a panel of 200 inbred and sequenced lines each founded with an individual wild-caught fly. We discovered a surprising level of variation in Rh5/Rh6 expression patterns and identified a number of informative genetic variants in genes known to play a role in photoreceptor differentiation and function. We are currently mapping additional genetic variants, which are likely to be new genes.
  • We began screening wild-caught flies and also identified interesting heritable phenotypes which we are mapping. Thus we have succeeded in every step required for identification of the genetic variant that underlies an interesting natural phenotype. Our results are beginning to reveal similarities in natural variation of human and fly retinal phenotypes. The accumulated experience allowed us to establish a collaboration with François Rouyer lab, seeking natural variants affecting the entrainment of circadian clock by light.

Natural variation of Drosophila Rh expression

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 human species, there is a surprising level of natural variation affecting the visual system. The ratios of different colour photoreceptors differ vastly among 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 the Drosophila natural 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 about the architecture of natural variation in the visual system.

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