Growth Control and Beyond: Functional Diversity and Regulation of the Hippo Pathway in the Nervous System

The Hippo pathway prevents tissue overgrowth and tumorigenesis in many organs across species. Not surprisingly, this pathway limits the proliferation of progenitor cells in diverse regions of the nervous system, and its dysregulation can lead to neural tumors in humans. However, the functions of the Hippo pathway extend beyond proliferation control. Recent studies have revealed a remarkable functional diversity across neural lineages, encompassing morphogenesis, cell fate, tissue maintenance, and repair. This review synthesizes current evidence on the roles and regulation of the Hippo pathway in neural progenitor cells, glial cells, and neurons, highlighting context-dependent mechanisms and outstanding questions. With the core molecular machinery and many fundamental cellular functions of the Hippo pathway now established, the field is entering a new phase: unraveling the functional significance and regulatory complexity of Hippo signaling in physiologically relevant contexts-both normal and diseased-promises to deepen our mechanistic understanding of neural development and homeostasis, and unlock new strategies for tumor therapy and neural repair.