Gauberg Julia, Jenkins Sarah, Moreno Kevin B, Jayaraman Karthik, Abumeri Sara, Salazar Alisa, Meharena Hiruy S, Glasgow Stacey M
Neurobiology Department, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Sci Adv. 2025 Aug;11(31):eadu3346. doi: 10.1126/sciadv.adu3346. Epub 2025 Aug 1.
Neural circuits governing all 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 muscle targeting. 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 adenosine triphosphate production, providing an 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.
支配脊椎动物所有运动行为的神经回路依赖于运动神经元的正常发育及其对肢体肌肉的精确靶向。转录因子对于运动神经元的发育至关重要,可调节其特化、迁移和轴突靶向。虽然运动神经元特化早期阶段的转录调控已得到充分证实,但对于转录因子在成熟后期和肌肉靶向中的作用却知之甚少。明确这些后期阶段的分子机制对于阐明运动回路的构建方式至关重要。在这里,我们证明转录因子核因子IA(NFIA)是运动神经元定位、轴突分支和神经肌肉接头形成所必需的。此外,我们发现NFIA是正常线粒体功能和三磷酸腺苷产生所必需的,这在运动神经元发育过程中提供了转录因子与代谢之间的重要联系。这些发现共同强调了NFIA在指导用于运动的脊髓回路组装中的关键作用。