Periodic Reporting for period 4 - NEUROMET (Shaping of axonal complexity by a dynamic regulation of local metabolic pathways in the developing cortex)
Período documentado: 2021-02-01 hasta 2022-07-31
The project NEUROMET aimed at better understanding how a local regulation of metabolic pathways underlie neuron development and circuit formation in the mouse neocortex. Our research combined cutting-edge microscopy methods, functional metabolomic analyses and models to identify and characterize the relationship between glucose metabolism and axon development. This project has provide new insights into the molecular mechanisms underlying the development of the neocortex as well as point out some of the consequences of metabolic imbalance on the development of the brain, a question that has many important implications for public health.
We have validated methods to measure and manipulate metabolic activity in cultured neurons. With this set of techniques, we contributed to demonstrate the central role of mitochondria in the regulation of cortical circuits complexity, and identified some of the molecular mechanisms involved, which constitute putative druggable targets (work in progress).
We uncovered how extracellular signals tied to the local regulation of axonal morphogenesis converge on the regulation of neuronal signaling pathways that are important for metabolic regulation in the developing brain.
We tested the relevance of polymorphisms identified in cohorts of patients suffering from neurodevelopmental disorders and demonstrated that the NUAK1 gene is haploinsufficient in regards to cortical circuits development and demonstrated the potential pathogenicity of mutations in this gene and associated to neurodevelopmental disorders.
Overall, this project led to 9 publications, and several other articles are in preparation. Two PhD students defended and earned a PhD with two more students still in progress.