Neuronal Hippo signaling: From development to diseases

Abstract

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.

Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain

“…Similarly, the Hippo Signaling pathway was significantly enriched in cLBP and PFC groups. This pathway plays a crucial role in neurodegenerative diseases and neuronal function by regulating neuronal growth and proliferation, differentiation, synaptogenesis, and apoptosis [ 57 , 58 ]. In animal models, Li and colleagues found that the expression of Hippo signaling pathway components (Yap and TAZ) play an essential role in neuropathic pain by regulating synaptic and structural plasticity [ 59 ].…”

Post-synaptic scaffold protein TANC2 in psychiatric and somatic disease risk

“…TANC2 is highly expressed during brain development and interacts with proteins from important developmental signalling pathways such as Wnt (PRICKLE1/2) and Hippo (ZYX, YWHAB, LATS2), as well as with proteins involved in cilium assembly (CBY1, CEP120) and trafficking (INPP5E) ( Gasparini et al, 2017 ). Both Wnt and Hippo pathway proteins can regulate, among other neurodevelopmental processes, dendritic arborisation and synapse formation ( Budnik and Salinas, 2011 ; Sahu and Mondal, 2021 ). Thus, TANC2 can influence synaptic function through interaction with these pathways leading to NDDs.…”

Emerging roles for the YAP/TAZ transcriptional regulators in brain tumour pathology and targeting options

“…Moreover, NPCs differentiation is also induced by FAT4‐DACHS, which further inhibit YAP/TAZ activity 31 . The inhibition of YAP/TAZ by Hippo has been shown to promote neuritogenesis, the sprouting of neurites from neurons, prior to establishment of functional interneural synapses 37 . YAP/TAZ also participate in the programming of neural cell apoptosis.…”

“…YAP/TAZ also participate in the programming of neural cell apoptosis. Under stressful conditions, the Hippo pathway becomes overactivated, 37 leading to the retainment of YAP in the cytoplasm by interacting with 14‐3‐3 or p73 in the nucleus and induction of apoptosis 38,39 …”