Roome Robert Brian, Yadav Archana, Flores Lydia, Puarr Amrit, Nardini Diana, Richardson Alexander, Waclaw Ronald R, Arkell Ruth M, Menon Vilas, Johnson Jane E, Levine Ariel J
Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
bioRxiv. 2025 Mar 15:2025.03.14.643370. doi: 10.1101/2025.03.14.643370.
The dorsal horn of the mammalian spinal cord is an exquisite example of form serving function. It is comprised of diverse neuronal populations stacked into laminae, each of which receives different circuit connections and plays specialized roles in behavior. An outstanding question is how this organization emerges during development from an apparently homogeneous pool of neural progenitors. Here, we found that dorsal neurons are diversified by time, with families of related cell types born as temporal cohorts, and by a spatial-molecular gradient that specifies the full array of individual cell types. Excitatory dorsal neurons then settle in a chronotopic arrangement that transforms their progressive birthdates into anatomical order. This establishes the dorsal horn laminae, as these neurons are also required for spatial organization of inhibitory neurons and sensory axons. This work reveals essential ontogenetic principles that shape dorsal progenitors into the diverse cell types and architecture that subserve sensorimotor behavior.
哺乳动物脊髓背角是形式服务于功能的一个精妙典范。它由堆叠成层的多种神经元群体组成，每一层都接收不同的神经回路连接，并在行为中发挥特定作用。一个突出的问题是，这种组织结构在发育过程中是如何从看似同质的神经祖细胞池中形成的。在这里，我们发现背侧神经元在时间上是多样化的，相关细胞类型家族作为时间群组产生，并且通过一种空间分子梯度来确定所有个体细胞类型。然后，兴奋性背侧神经元以一种时间定位的排列方式定居下来，将它们逐渐的出生日期转化为解剖学顺序。这就建立了背角层，因为这些神经元对于抑制性神经元和感觉轴突的空间组织也是必需的。这项工作揭示了塑造背侧祖细胞成为服务于感觉运动行为的多种细胞类型和结构的基本个体发生原则。
