Pelenyi Alexandra, Atterton Cooper, Jones Justin, Currey Laura, Al-Khalily Majd, Wright Lucinda, Kurniawan Nyoman D, Thor Stefan, Piper Michael
The School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, QLD, 4072, Australia.
The Centre for Advanced Imaging, The University of Queensland, QLD, 4072, Australia.
Gene Expr Patterns. 2024 Dec;54:119384. doi: 10.1016/j.gep.2024.119384. Epub 2024 Nov 16.
The Hippo pathway is a critical regulator of animal development. Activation of the Hippo pathway causes a cascade of phosphorylation events that culminate in the phosphorylation of the transcriptional co-factors YAP and TAZ, which limits their entry into the nucleus. When the Hippo pathway is 'off', however, YAP and TAZ can enter the nucleus, where they interact with the transcription factors of the TEA Domain (TEAD) family to regulate transcriptional activity. Despite the importance of the Hippo pathway for development, including within the nervous system, the expression of the TEAD family remains poorly defined in mammals. Here, we mapped the expression of TEAD1 in the developing mouse brain. We find that TEAD1 expression is confined to progenitor cells during embryonic development, namely radial glia and intermediate progenitor cells. TEAD1 expression is not evident in post-mitotic neurons of the cortical plate. We also identify expression of TEAD1 in developing and mature ependymal cells of the lateral and third ventricle, including within the subcommissural organ, as well as by cells within the choroid plexuses and the forebrain neurogenic niches. Finally, we find that adult mice conditionally heterozygous for Tead1 in the central nervous system exhibit a significantly smaller brain. Collectively, these findings reveal a specific pattern of expression for TEAD1 during telencephalic development and implicate this factor in regulating neural progenitor cell proliferation.
河马通路是动物发育的关键调节因子。河马通路的激活会引发一系列磷酸化事件，最终导致转录辅因子YAP和TAZ的磷酸化，这限制了它们进入细胞核。然而，当河马通路“关闭”时，YAP和TAZ可以进入细胞核，在那里它们与TEA结构域（TEAD）家族的转录因子相互作用，以调节转录活性。尽管河马通路对包括神经系统在内的发育很重要，但TEAD家族在哺乳动物中的表达仍不清楚。在这里，我们绘制了TEAD1在发育中的小鼠大脑中的表达图谱。我们发现，在胚胎发育过程中，TEAD1的表达仅限于祖细胞，即放射状胶质细胞和中间祖细胞。在皮质板的有丝分裂后神经元中，TEAD1的表达不明显。我们还确定了TEAD1在侧脑室和第三脑室发育和成熟的室管膜细胞中的表达，包括在联合下器官内，以及脉络丛和前脑神经发生微环境中的细胞。最后，我们发现，在中枢神经系统中条件性杂合缺失Tead1的成年小鼠大脑明显较小。总的来说，这些发现揭示了TEAD1在端脑发育过程中的特定表达模式，并表明该因子在调节神经祖细胞增殖中起作用。
