Bateman Joseph M
Wolfson Center for Age-Related Diseases, King's College London ; London, UK.
Neurogenesis (Austin). 2015 Nov 13;2(1):e1058684. doi: 10.1080/23262133.2015.1058684. eCollection 2015.
Temporal control of neuronal differentiation is critical to produce a complete and fully functional nervous system. Loss of the precise temporal control of neuronal cell fate can lead to defects in cognitive development and to disorders such as epilepsy and autism. Mechanistic target of rapamycin (mTOR) is a large serine/threonine kinase that acts as a crucial sensor of cellular homeostasis. mTOR signaling has recently emerged as a key regulator of neurogenesis. However, the mechanism by which mTOR regulates neurogenesis is poorly understood. In constrast to other functions of the pathway, 'neurogenic mTOR pathway factors' have not previously been identified. We have very recently used Drosophila as a model system to identify the gene unkempt as the first component of the mTOR pathway regulating neuronal differentiation. Our study demonstrates that specific adaptor proteins exist that channel mTOR signaling toward the regulation of neuronal cell fate. In this Commentary we discuss the role of mTOR signaling in neurogenesis and the significance of these findings in advancing our understanding of the mechanism by which mTOR signaling controls neuronal differentiation.
神经元分化的时间控制对于产生一个完整且功能齐全的神经系统至关重要。神经元细胞命运精确时间控制的丧失会导致认知发育缺陷以及癫痫和自闭症等疾病。雷帕霉素机制性靶标（mTOR）是一种大型丝氨酸/苏氨酸激酶，作为细胞稳态的关键传感器。mTOR信号传导最近已成为神经发生的关键调节因子。然而，mTOR调节神经发生的机制尚不清楚。与该通路的其他功能不同，“神经源性mTOR通路因子”此前尚未被鉴定。我们最近利用果蝇作为模型系统，鉴定出蓬乱基因是mTOR通路调节神经元分化的首个组成部分。我们的研究表明，存在特定的衔接蛋白，它们将mTOR信号导向对神经元细胞命运的调节。在本述评中，我们讨论了mTOR信号传导在神经发生中的作用以及这些发现对于推进我们对mTOR信号传导控制神经元分化机制理解的意义。
