Organelle interaction in neuron function and neurodevelopment of Drosophila

Neurodevelopment is a fundamental process that shapes the functionality and wiring of the adult brain. Its two premises are growth (for axon elongation) and connection (finding a synaptic partner) that involve both extracellular cues and intracellular processes. Subcellular compartments, the organelles, are indispensable for providing material and energy for growth and for the trafficking of synaptic proteins. Many organelles, such as the endoplasmic reticulum (ER), mitochondria and endosomes/lysosomes disperse throughout the neuronal compartments, soma, axon and dendrites.

Our research focuses on three subcellular processes that shape neuron function and neurodevelopment:

• We described a role for ER-mitochondria contacts in the formation of mitochondrial hydrogen peroxide and showed that it is required for the activity of dopaminergic neurons. This ultimately determines locomotion.
• We found that peroxisomes, despite their interconnection with other organelles by membrane contact sites, are restricted to somata in differentiated neurons. Moreover, we identified a narrow developmental time window that is characterized by a “peroxisomal burst”. In this period, peroxisomes are highly dynamic, abundant and spread through all neuronal compartments. Inhibition of peroxisome biogenesis blocks the transport of synaptic proteins to their destination and impacts on neuronal distribution of other organelles such as mitochondria. The time and space distribution of peroxisomes thus constitutes an undescribed, yet fundamental process in neurodevelopment.
• Peroxisomes play a so far undescribed role in the secretion of neuropeptides. We found that they interact with the Golgi apparatus and determine the lipid composition of secretory vesicles.  Additionally, we found that peroxisomes are required for neuropeptide secretion by interaction with the Golgi apparatus.  

We use Drosophila melanogaster as a model organism that allows us to study neuronal organelle communication in vivo and to assess its impact on the organismal level.

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