TRPV4 and DISC1: regulators of cytoskeletal control in microglia

Abstract

Microglia are the primary immune cells of the central nervous system, and their functions are essential for proper brain development, maintenance, and health. During embryogenesis, these cells colonize the brain and adopt a ramified, surveillant phenotype in the healthy adult brain. Throughout life, microglia are uniquely positioned to respond dynamically to their environment, allowing them to contribute to key physiological processes such as synaptic pruning, neurogenesis, angiogenesis, and maintenance of brain cell homeostasis. These roles rely on microglial motility, ranging from cell migration to the dynamic remodeling of their processes. Impairments in microglial function are increasingly associated with brain malformations and neurological disorders, including Alzheimer’s disease, autism spectrum disorder, and schizophrenia. Developmental disruptions in microglial function can lead to long-term consequences that alter the brain’s ability to respond to infection and process cognitive information in adulthood. This highlights the importance of understanding the mechanisms that regulate microglial motility and function throughout life. Despite the established importance of microglial motility in brain development and homeostasis, the cellular and molecular mechanisms underlying their migration, morphology, and immune functions remain incompletely understood. This doctoral dissertation aims to address this gap by focusing on two proteins that govern cytoskeletal remodeling in microglia, particularly in pathological conditions.