Regulation of neuronal morphology: Exploring the function of Ral GTPase in nerve thickness and in structural plasticity

• Autor(a) principal: Santos, Beatriz Figueiras dos
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/26415
• topic: Ral GTPase; JNK; Structural plasticity; Nerve thickness; Drosophila; FasII; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Neurons are the most morphologically diverse cell type whose development and maintenance are essential for proper function of the nervous system. The primary shape of a neuron is established during axon and dendrite outgrowth and synapse formation, but is subject to subsequent modifications by physiological events. Ral is a small GTPase, member of the Ras superfamily that is known to play an important role in a plethora of biological processes such as the regulation of structural plasticity in the postsynaptic compartment. Here, we aim to understand the involvement of Ral GTPase in the regulation of presynaptic structural plasticity, by studying its role in the formation of new synaptic boutons in response to activity. An important aspect of nervous system development concerns how axons are organized into nerve bundles. When exiting the Central Nervous System (CNS), axons from several neurons are bundled together to innervate different muscles in a stereotyped manner. Here, we show that Drosophila Ral GTPase regulates nerve thickness and organization. Ral mutants have thicker nerve bundles and decreased levels of Fasciclin II, a cell adhesion molecule, suggesting that possibly, there is a defect in axonal fasciculation. Ral GTPase has been shown to be a positive or negative regulator of JNK signaling, depending on the cellular context, while JNK signaling has been shown to be involved in axon pruning by destabilization of the cell adhesion protein FasII. We want to understand if Ral regulates nerve thickness via JNK, via cell adhesion modulation, and whether its function is required in neurons and/or glia. Glial cells are an integral part of the nervous system and play an important role in the regulation of neuronal development and function. Our results suggest that Ral does not interact with JNK signaling in neurons or in glial cells to regulate nerve thickness. However, the role of Ral in glia appears to play a role in the regulation of nerve thickness. Thus, it is critical to understand how glial cells regulate nerve thickness and what are the pathways involved in this process since defects in neuronal and glia morphology are a hallmark of several neurodevelopmental and neurodegenerative disorders.