Abstract

Establishment of functional neuronal circuits during development requires proper specification of cell types, their precise positioning within the brain, interplay with other cell types or extracellular matrix, as well as formation and pruning of synapses.

In this symposium, we will discuss how molecular mechanisms of protein synthesis and homeostasis organize functional circuit architecture at various levels of (sub)cellular organization and their relevance to brain disorders. We will explore how local and global protein synthesis and proteostatic regulation affect the development and integrity of the nervous system. The discussion will revolve around the assembly of neuronal circuits driven by tightly controlled remodeling of protein landscapes in cellular ensembles using different model organisms, including C. elegans and M. musculus. We will shed light on the inherent translation dynamics in distinct types of glutamatergic neurons, and the consequences of disruption to the protein synthesis pathways early in development for brain wiring. It will be demonstrated how local transcriptomes define synaptic subpopulations to drive pruning and how this process relates to neuropathology. Finally, we will show evidence that the robustness of functional neuronal circuits in age-progression relies on the integrity and biomechanics of the extracellular matrix, controlled by chaperone-driven proteostasis.

In our talks, we will showcase cutting-edge genetic and proteomic technologies and real-time imaging at cellular and subcellular resolution to uncover the mechanisms fine-tuning the proteome and its homeostasis. This symposium highlights different modes of gene expression regulation at various levels of spatiotemporal organization and emphasizes that (post)-translational regulation plays indispensable roles in virtually every milestone of neuronal circuit development and function.