Developing zebrafish models of Notch-related CNS pathologies

Notch signaling is an evolutionarily conserved cellular pathway that regulates various stem cell functions, including fate determination, differentiation, proliferation, and apoptosis. This crucial signaling mechanism also plays an important role in the brain, regulating neurogenesis, cell differentiation, and homeostasis, whereas disrupted Notch signaling is linked to various neurodegenerative diseases and brain cancers. Here, we review the central nervous system (CNS) pathologies associated with aberrant Notch signaling, and summarize the available experimental (animal) models used to study these pathologies, with a special focus on zebrafish (Danio rerio). As genetic, pharmacological, and behavioral models in zebrafish have significantly advanced our understanding of Notch-related CNS disorders, future research is expected to further link Notch signaling to brain disorders and, eventually, lead to their more specific and targeted therapeuties.