Liquid–liquid phase separation in neural development

Liquid–liquid phase separation (LLPS) is a physicochemical process in which a homogeneous mixture of molecules separates into a denser phase originating from preferential self-assembly, driven by multivalent interactions, frequently mediated by intrinsically disordered protein regions, RNAs, or structured modular domains. LLPS produces a large variety of nuclear or cytoplasmic membrane-less biomolecular condensates with liquid-like properties. The importance of LLPS in several aspects of neural development and function is now supported by numerous studies. In this review we describe the findings supporting the importance of LLPS in different aspects of neural development, including asymmetric division of neural progenitors, chromatin remodeling and transcriptional/post-transcriptional control, localized translation and regeneration of neurites, and synaptic organization and function. We will focus especially on studies supporting the implication of LLPS in vivo. Finally, we will consider the important implication of LLPS-driven mechanisms as causes of neurodevelopmental and neurodegenerative diseases.