GLIALIFE

In vertebrate and invertebrate brains, neurons establish regionally distinct circuit architectures. Astrocytes are crucial elements in this environment, displaying remarkably elaborate, yet specific branching patterns. However, how astrocytes acquire their diverse morphologies in interaction with neurons and how these shape neuronal morphologies and function remains poorly understood. Our study will use the Drosophila visual system as an in vivo model, focusing on the interactions of neurons and astrocyte-like glia in the medulla. The latter establish stereotypic columnar and layer-specific branching patterns during development. Previously, we have shown that the glial-specific transmembrane Leucine-rich repeat protein Lapsyn is required for astrocyte branch extension into the synaptic neuropil. Using label-free mass spectrometry, we isolated a member of the Innexin family as one potential binding partner of Lapsyn. Based on our genetic analysis, we hypothesize that neuron subtypes engage in a dialog with astrocytes through gap junctions, that are stabilized by Lapsyn, to establish correct local glial morphologies. These in turn could refine neuronal development and function. In this integrative project from development to function, we will employ tailored genetic tools to achieve cell-type specific labeling and gene manipulations, as well as high-resolution and functional imaging. Specifically, our aims are (1) to characterize the developing neuron-astrocyte interface in the context of gap junction communication with specific neuron subtypes, (2) to assess the dynamic behavior of astrocyte branches during development, and (3) to examine how astrocyte branches shape synaptic connectivity and functional neuronal properties such as neurotransmitter recycling and axon initial segment proteins.