Kramer Ina, Sigrist Markus, de Nooij Joriene C, Taniuchi Ichiro, Jessell Thomas M, Arber Silvia
Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Neuron. 2006 Feb 2;49(3):379-93. doi: 10.1016/j.neuron.2006.01.008.
Subpopulations of sensory neurons in the dorsal root ganglion (DRG) can be characterized on the basis of sensory modalities that convey distinct peripheral stimuli, but the molecular mechanisms that underlie sensory neuronal diversification remain unclear. Here, we have used genetic manipulations in the mouse embryo to examine how Runx transcription factor signaling controls the acquisition of distinct DRG neuronal subtype identities. Runx3 acts to diversify an Ngn1-independent neuronal cohort by promoting the differentiation of proprioceptive sensory neurons through erosion of TrkB expression in prospective TrkC+ sensory neurons. In contrast, Runx1 controls neuronal diversification within Ngn1-dependent TrkA+ neurons by repression of neuropeptide CGRP expression and controlling the fine pattern of laminar termination in the dorsal spinal cord. Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification.
背根神经节(DRG)中的感觉神经元亚群可根据传递不同外周刺激的感觉模式来进行表征,但感觉神经元多样化背后的分子机制仍不清楚。在这里,我们利用对小鼠胚胎进行基因操作来研究Runx转录因子信号传导如何控制不同DRG神经元亚型身份的获得。Runx3通过在前体TrkC+感觉神经元中侵蚀TrkB表达来促进本体感觉神经元的分化,从而使不依赖Ngn1的神经元群体多样化。相比之下,Runx1通过抑制神经肽CGRP表达并控制背脊髓中层状终末的精细模式,来控制依赖Ngn1的TrkA+神经元内的神经元多样化。总之,我们的研究结果表明Runx转录因子信号传导在感觉神经元多样化中起关键作用。