Neurogenetics 520 -- Ataxia Telangciestca

Overview of Study

  • Focus on understanding the relationship between the STRING gene and ATM protein in neuron behavior.

  • Investigated the effects of 650 newtons of a specific condition on eye development in mutant Drosophila flies.

Key Concepts

Neuron Development and Mutations

  • Lemmatidia Rows: Observed fewer nerve degeneration signs (degenerated photoreceptor neurons) with specific size comparisons in eyes.

  • Mutants: Identified six different mutants, including suppressors and STRING (cd c15) gene affecting cell cycle regulation.

Role of STRING in Cell Cycle

  • Cell Cycle Phases: G1 phase (diploid, 2n), S phase (DNA replication, 4n), G2 phase, mitosis.

  • STRING promotes transition from G1 to S phase, preventing excessive cell division in neurons, which are typically post-mitotic.

  • Loss of ATM inhibits STRING's ability to facilitate the G1 to S transition, hence preventing unwanted neuron proliferation.

Experimental Observations

DNA Content Measurement

  • Employ FAC (Fluorescent Activated Cell Sorting) to quantify DNA levels in cells from the eye imaginal disc.

  • Assuming neurons should only maintain 2n DNA content unless undergoing replication.

Genetic Experiments

  • Used heterozygous mutations for ATM to study cell cycle re-entry in neurons.

  • Predicted and confirmed STRING mutations reduced cell cycle re-entry phenotype associated with reduced ATM function.

Conclusions and Future Directions

  • Loss of ATM may lead to inappropriate cell cycle re-entry and has implications for DNA damage responses in neurons.

  • Examined connections between cell cycle regulation and innate immune responses in the brain, with some speculation towards potential therapeutic applications of ATM mutations in disease contexts.

  • Further research needed on the relationship between immune responses and cell cycle behaviors in neurons.