University Côte d'Azur, CNRS, Inserm, iBV, Nice 06108, France.
Institute of Basic Medical Sciences, University of Oslo, Oslo N-0317, Norway.
Development. 2022 Mar 1;149(5). doi: 10.1242/dev.200026. Epub 2022 Mar 9.
Axonal projections from layer V neurons of distinct neocortical areas are topographically organized into discrete clusters within the pontine nuclei during the establishment of voluntary movements. However, the molecular determinants controlling corticopontine connectivity are insufficiently understood. Here, we show that an intrinsic cortical genetic program driven by Nr2f1 graded expression is directly implicated in the organization of corticopontine topographic mapping. Transgenic mice lacking cortical expression of Nr2f1 and exhibiting areal organization defects were used as model systems to investigate the arrangement of corticopontine projections. By combining three-dimensional digital brain atlas tools, Cre-dependent mouse lines and axonal tracing, we show that Nr2f1 expression in postmitotic neurons spatially and temporally controls somatosensory topographic projections, whereas expression in progenitor cells influences the ratio between corticopontine and corticospinal fibres passing the pontine nuclei. We conclude that cortical gradients of area-patterning genes are directly implicated in the establishment of a topographic somatotopic mapping from the cortex onto pontine nuclei.
在自愿运动形成过程中，来自不同新皮质区域的 V 层神经元的轴突投射在前脑桥核中被组织成离散的簇。然而，控制皮质脑桥连接的分子决定因素还不够了解。在这里，我们表明，由 Nr2f1 梯度表达驱动的固有皮质遗传程序直接参与了皮质脑桥拓扑图的组织。作为模型系统，我们使用缺乏皮质 Nr2f1 表达且表现出区域组织缺陷的转基因小鼠来研究皮质脑桥投射的排列。通过结合三维数字大脑图谱工具、 Cre 依赖性小鼠系和轴突追踪，我们表明，Nr2f1 在有丝分裂后神经元中的表达在空间和时间上控制躯体感觉的拓扑投射，而在前体细胞中的表达影响穿过脑桥核的皮质脑桥和皮质脊髓纤维之间的比例。我们得出结论，皮质区域形成基因的梯度直接参与了从皮质到脑桥核的躯体感觉拓扑映射的建立。
