Mohylyak Iryna, Bengochea Mercedes, Pascual-Caro Carlos, Asfogo Noemi, Fonseca-Topp Sara, Danda Natasha, Atak Zeynep Kalender, De Waegeneer Maxime, Plaçais Pierre-Yves, Preat Thomas, Aerts Stein, Corti Olga, de Juan-Sanz Jaime, Hassan Bassem A
bioRxiv. 2023 Jun 11:2023.06.11.544500. doi: 10.1101/2023.06.11.544500.
During neuronal circuit formation, local control of axonal organelles ensures proper synaptic connectivity. Whether this process is genetically encoded is unclear and if so, its developmental regulatory mechanisms remain to be identified. We hypothesized that developmental transcription factors regulate critical parameters of organelle homeostasis that contribute to circuit wiring. We combined cell type-specific transcriptomics with a genetic screen to discover such factors. We identified Telomeric Zinc finger-Associated Protein (TZAP) as a temporal developmental regulator of neuronal mitochondrial homeostasis genes, including . In , loss of function during visual circuit development leads to loss of activity-dependent synaptic connectivity, that can be rescued by expression. At the cellular level, loss of leads to defects in mitochondrial morphology, attenuated calcium uptake and reduced synaptic vesicle release in fly and mammalian neurons. Our findings highlight developmental transcriptional regulation of mitochondrial homeostasis as a key factor in activity-dependent synaptic connectivity.
在神经元回路形成过程中，轴突细胞器的局部控制确保了适当的突触连接。这个过程是否由基因编码尚不清楚，如果是这样，其发育调控机制仍有待确定。我们假设发育转录因子调节细胞器稳态的关键参数，这些参数有助于回路布线。我们将细胞类型特异性转录组学与基因筛选相结合来发现此类因子。我们鉴定出端粒锌指相关蛋白（TZAP）是神经元线粒体稳态基因的一个时间发育调节因子，包括 。在 中，视觉回路发育过程中 功能的丧失导致依赖活动的突触连接丧失，而 的表达可以挽救这种情况。在细胞水平上， 的缺失导致线粒体形态缺陷、钙摄取减弱以及果蝇和哺乳动物神经元中突触小泡释放减少。我们的研究结果突出了线粒体稳态的发育转录调控作为依赖活动的突触连接的关键因素。
