The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.

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Aim: To study the damaging effect of chronic ingestion of 20 mg/kg body weight/OD of lithium carbonate on cerebellargranule cells. Methods: However, there is scanty documented information about the cerebellar toxicities of lithium carbonate on granule neurons. Therefore the present study is designed to observe the microscopic changes of granule neurons in rat cerebellum. For this experimental study 20 animals were used, they were divided into two groups, each comprising of 10 animals. Results: Group-A received normal lab diet and water ad libitum while group B received lithium carbonate 20 mg/kg/OD for 2 weeks and 6 weeks respectively. Micrometry was done on granule cells count. Conclusion: Highly significant changes of granule cells count were observed even at therapeutic doses. Lithium carbonate causes oxidant injury to granule neuronal cells in rat cerebellum. Keywords: Oxidant injury, Cerebellar degeneration, Incoordination,

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