A carregar...
Publicação
Effect of neuronal extracellular factors on synapse formation : how glia contribute to neuronal structure and function during development
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 3 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
The ability to think, move, or sense the environment relies on the proper development and wiring of the nervous system. Neurons communicate via specialized structures, called synapses, which are assembled within synaptic boutons - conserved axonal specializations where synapses are housed. Neurons can change morphology in response to synaptic activity, a process known as synaptic plasticity. While the intrinsic neuronal mechanisms behind synapse formation and plasticity are well described, a comprehensive three dimensional (3D) understanding of the surrounding cellular and extracellular environment, including glia, muscle, and the extracellular matrix (ECM), is still limited. Making use of the advantages of the Drosophila melanogaster larval neuromuscular junction (NMJ) this thesis aims to unravel how glial cells, in particular perineurial glia (PG) and subperineurial glia (SPG), contribute to neuronal structure, maintenance, and plasticity. By fluorescently labeling both PG and SPG in the same larvae we were able to directly compare their morphologies at the NMJ, revealing distinct morphologies and spatial distributions, suggesting different specialized functions. SPG occupied larger areas and extended processes into synaptic regions, whereas PG area was more variable, sometimes forming protrusions toward trachea, hinting at a possible metabolic function. Targeted genetic ablation of SPG led to disruptions in motor neuron morphology, including axonal fragmentation, bouton enlargement and reduced neuronal size, and impaired larval locomotion demonstrating that SPG has a role in preserving neuronal integrity, structure and function. Finally, by knocking down matrix metalloproteinases (Mmp1 and Mmp2) in neurons and glia we discovered that new bouton formation was hindered, suggesting that both neurons and glia can regulate plasticity, likely by modulating ECM remodeling. Together, these findings further reaffirm the role of glial cells in shaping neuronal development and plasticity, establish SPG as key regulators of NMJ structural integrity, and highlight neuron–glia–ECM interactions as drivers of synaptic plasticity.
Descrição
Tese de Mestrado, Biologia do Organismo e Evolução, 2026, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Drosophila Neuromuscular Junction Glial Cells Synaptic Formation Synaptic Plasticity