Spinal motor neuron development and metabolism are transcriptionally regulated by Nuclear Factor IA [RNA-Seq]. Spinal motor neuron development and metabolism are transcriptionally regulated by Nuclear Factor IA [RNA-Seq]

Neural circuits governing complex motor behaviors in vertebrates rely on the proper development of motor neurons and their precise targeting of limb muscles. Transcription factors are essential for motor neuron development, regulating their specification, migration, and axonal targeting. While transcriptional regulation of the early stages of motor neuron specification is well-established, much less is known about the role of transcription factors in the later stages of maturation and terminal arborization. Defining the molecular mechanisms of these later stages is critical for elucidating how motor circuits are constructed. Here, we demonstrate that the transcription factor Nuclear Factor-IA (NFIA) is required for motor neuron positioning, axonal branching, and neuromuscular junction formation. Moreover, we find that NFIA is required for proper mitochondrial function and ATP production, providing a new and important link between transcription factors and metabolism during motor neuron development. Together, these findings underscore the critical role of NFIA in instructing the assembly of spinal circuits for movement. Overall design: To investigate the function of NFIA in mouse motor neuron development, we knocked down NFIA from the CNS. We performed gene expression profiling from 3 control and 3 conditional knockout E13.5 embryos.

脊椎动物中调控复杂运动行为的神经环路，依赖于运动神经元（Motor Neuron）的正常发育及其对肢体肌肉的精准靶向投射。转录因子（Transcription Factor）对于运动神经元发育至关重要，可调控其细胞命运特化、迁移以及轴突靶向投射。尽管运动神经元特化早期阶段的转录调控机制已被广泛阐明，但学界对转录因子在运动神经元成熟及轴突终末分枝的后期阶段所发挥的作用仍知之甚少。阐明这些后期阶段的分子机制，对于解析运动环路的构建过程至关重要。本研究证实，转录因子核因子IA（Nuclear Factor-IA, NFIA）在运动神经元定位、轴突分支及神经肌肉接头（Neuromuscular Junction）形成过程中不可或缺。此外，本研究发现NFIA对于维持正常的线粒体功能与ATP生成亦不可或缺，这为运动神经元发育过程中转录因子与代谢之间的关联提供了全新的重要线索。综上，这些研究结果凸显了NFIA在指导脊髓运动环路组装以实现运动功能中的关键作用。整体实验设计：为探究NFIA在小鼠运动神经元发育中的功能，我们从中枢神经系统（Central Nervous System, CNS）中敲低了NFIA的表达。我们对3只对照组胚胎与3只条件性敲除的E13.5胚胎进行了基因表达谱分析。