Neuronal Hippo signaling: From development to diseases

Dev Neurobiol. 2021 Mar;81(2):92-109. doi: 10.1002/dneu.22796. Epub 2020 Dec 12.


Hippo signaling pathway is a highly conserved and familiar tissue growth regulator, primarily dealing with cell survival, cell proliferation, and apoptosis. The Yes-associated protein (YAP) is the key transcriptional effector molecule, which is under negative regulation of the Hippo pathway. Wealth of studies have identified crucial roles of Hippo/YAP signaling pathway during the process of development, including the development of neuronal system. We provide here, an overview of the contributions of this signaling pathway at multiple stages of neuronal development including, proliferation of neural stem cells (NSCs), migration of NSCs toward their destined niche, maintaining NSCs in the quiescent state, differentiation of NSCs into neurons, neuritogenesis, synaptogenesis, brain development, and in neuronal apoptosis. Hyperactivation of the neuronal Hippo pathway can also lead to a variety of devastating neurodegenerative diseases. Instances of aberrant Hippo pathway leading to neurodegenerative diseases along with the approaches utilizing this pathway as molecular targets for therapeutics has been highlighted in this review. Recent evidences suggesting neuronal repair and regenerative potential of this pathway has also been pointed out, that will shed light on a novel aspect of Hippo pathway in regenerative medicine. Our review provides a better understanding of the significance of Hippo pathway in the journey of neuronal system from development to diseases as a whole.

Keywords: Hippo signaling; brain development; neural stem cells; neurodegeneration; neuronal development; neuronal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation
  • Cell Proliferation
  • Hippo Signaling Pathway*
  • Humans
  • Neurodegenerative Diseases*
  • Signal Transduction / genetics