The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine‐threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.

中文翻译：

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Tao在果蝇的神经肌肉连接发育过程中负调控BMP信号传导。

突触的协调生长和发育对于神经回路功能的各个方面都至关重要，破坏这些过程的突变可能导致各种神经系统缺陷。几种顺行和逆行信号传导途径，包括规范的骨形态发生蛋白（BMP）途径，可调节脊椎动物和无脊椎动物的突触发育。在果蝇幼虫神经肌肉连接处（NMJ），逆行BMP途径是控制NMJ与幼虫生长同时进行的机制的一部分。我们试图确定保守的Hippo通路对其他组织的比例生长至关重要，它是否也可在NMJ发育中起作用。我们发现丝氨酸-苏氨酸蛋白激酶Tao的神经元丢失，河马信号通路的调节剂，导致多余的按钮，其中包含正常密度的活动区。陶也需要适当的突触功能，因为减少陶氏会导致诱发兴奋性连接神经节电位降低的NMJ。出乎意料的是，陶氏功能在NMJ生长中独立于河马途径。相反，我们的实验表明，Tao负调节BMP信号，因为Tao的减少导致运动神经元核中pMad水平的增加和BMP目标基因表达的增加。综上所述，这些结果证明了陶的作用 作为突触发展和功能过程中运动神经元中BMP信号传导的新型抑制剂。