The Hippo effector TEAD1 regulates postnatal murine cerebellar development

• DOI: 10.1007/s00429-025-02903-x
• Publication Date: 2025-03-10T20:33:32Z
• Authors: Cooper Atterton; Alexandra Pelenyi; Justin Jones; Laura Currey; Majd Al-Khalily; Lucinda Wright; Mikki Doonan; David Knight; Nyoman D. Kurniawan; Shaun Walters; Stefan Thor; Michael Piper

Abstract The Hippo signalling cascade is an evolutionarily conserved pathway critical for the development of numerous organ systems and is required for the development of many parts of the mammalian nervous system, including the cerebellum. The Hippo pathway converges, via the nuclear YAP/TAZ co-transcription factors, on transcription factors of the TEA Domain (TEAD) family (TEAD1-4) and promotes the expression of pro-proliferative genes. Despite the importance of TEAD function, our understanding of spatial and temporal expression of this family is limited, as is our understanding of which TEAD family members regulate Hippo-dependent organ development. Here, we focus on TEAD1 and how this factor contributes to postnatal murine cerebellar development. We find expression of TEAD1 within cerebellar progenitor cells and glial cells, including astrocytes and Bergmann glia, as well as by some interneurons within the granular layer. The importance of TEAD1 expression for cerebellar development was investigated using a conditional ablation approach, which revealed a range of developmental deficits in Tead1 mutants, including an underdeveloped cerebellum, morphological defects in Bergmann Glia and Purkinje Neurons, as well as granule neuron migration defects. Collectively, these findings suggest a major role for TEAD1 as an effector of the Hippo pathway during cerebellar development.