Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Laboratory of Mammalian Neural Circuits, National Institute of Genetics, Mishima, Japan.
Elife. 2022 Mar 15;11:e67549. doi: 10.7554/eLife.67549.
Neuronal abundance and thickness of each cortical layer are specific to each area, but how this fundamental feature arises during development remains poorly understood. While some of area-specific features are controlled by intrinsic cues such as morphogens and transcription factors, the exact influence and mechanisms of action by cues extrinsic to the cortex, in particular the thalamic axons, have not been fully established. Here, we identify a thalamus-derived factor, VGF, which is indispensable for thalamocortical axons to maintain the proper amount of layer 4 neurons in the mouse sensory cortices. This process is prerequisite for further maturation of the primary somatosensory area, such as barrel field formation instructed by a neuronal activity-dependent mechanism. Our results provide an actual case in which highly site-specific axon projection confers further regional complexity upon the target field through locally secreting signaling molecules from axon terminals.
神经元数量和各皮层层的厚度因区域而异，但这一基本特征在发育过程中是如何产生的，目前仍知之甚少。虽然某些区域特有的特征受到内在信号（如形态发生素和转录因子）的控制，但皮层外的外在信号（特别是丘脑轴突）的确切影响和作用机制尚未完全确定。在这里，我们鉴定出一种来自丘脑的因子 VGF，它对于丘脑皮质轴突在小鼠感觉皮层中维持适当数量的第 4 层神经元是必不可少的。这个过程是初级体感区进一步成熟的前提，例如通过神经元活动依赖性机制指导的桶状皮层形成。我们的结果提供了一个实际的例子，即高度特异性的轴突投射通过从轴突末梢局部分泌信号分子，为靶场赋予了进一步的区域复杂性。
