Evolving Insights into Prickle2 in Neurodevelopment and Neurological Disorders.

Abstract

The development of neural circuits is a complex, highly coordinated process crucial for the proper functioning of the nervous system. This process involves the intricate interplay of numerous genes and signaling pathways. Prickle2, a protein encoded by the planar cell polarity (PCP) genes, is a key component of the noncanonical Wnt/PCP signaling pathway and plays a critical role in neural circuit development. Recent studies have highlighted the essential functions of Prickle2 in various stages of neural circuit formation, including the development of the initial segment of neuronal axons, axon elongation and regeneration, dendrite formation, synapse formation, and vesicle transport. The normal expression and spatial distribution of Prickle2 are vital for these processes, and its dysregulation has been associated with several neurological disorders, including congenital neural tube defects, Alzheimer's disease, epilepsy, and autism spectrum disorders. This review aims to systematically summarize the upstream and downstream signaling pathways and regulatory interactions involving Prickle2 in neurodevelopment and neural circuit formation. By discussing the expression patterns of Prickle2 in neurodevelopment and its associations with neurological diseases, we provide insights into the mechanisms through which Prickle2 influences neurodevelopment and its potential implications in neurological disorders.