Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces.

Cells are biochemically and morphologically polarized, which allows them to produce different cell shapes for various functions. Remarkably, some polarity protein complexes are asymmetrically recruited and concentrated on limited membrane regions, which is essential for the establishment and maintenance of diverse cell polarity. Though the components and mutual interactions within these protein complexes have been extensively investigated, how these proteins autonomously concentrate at local membranes and whether they have the same organization mechanism in the condensed assembly as that in aqueous solution remain elusive. A number of recent studies suggest that these highly concentrated polarity protein assemblies are membraneless biomolecular condensates which form through liquid–liquid phase separation (LLPS) of specific proteins. In this perspective, we summarize the LLPS-driven condensed protein assemblies found in asymmetric cell division, epithelial cell polarity, and neuronal synapse formation and function. These findings suggest that LLPS may be a general strategy for cells to achieve local condensation of specific proteins, thus establishing cell polarity.