Department of Neurobiology, University of California, Los Angeles, Los Angeles, California, USA.
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California, USA.
WIREs Mech Dis. 2021 Sep;13(5):e1520. doi: 10.1002/wsbm.1520. Epub 2021 Feb 25.
The spinal cord is functionally and anatomically divided into ventrally derived motor circuits and dorsally derived somatosensory circuits. Sensory stimuli originating either at the periphery of the body, or internally, are relayed to the dorsal spinal cord where they are processed by distinct classes of sensory dorsal interneurons (dIs). dIs convey sensory information, such as pain, heat or itch, either to the brain, and/or to the motor circuits to initiate the appropriate response. They also regulate the intensity of sensory information and are the major target for the opioid analgesics. While the developmental mechanisms directing ventral and dorsal cell fates have been hypothesized to be similar, more recent research has suggested that dI fates are specified by novel mechanisms. In this review, we will discuss the molecular events that specify dorsal neuronal patterning in the spinal cord, thereby generating diverse dI identities. We will then discuss how this molecular understanding has led to the development of robust stem cell methods to derive multiple spinal cell types, including the dIs, and the implication of these studies for treating spinal cord injuries and neurodegenerative diseases. This article is categorized under: Neurological Diseases > Stem Cells and Development.
脊髓在功能和解剖上可分为腹侧衍生的运动回路和背侧衍生的躯体感觉回路。起源于身体外周或内部的感觉刺激被传递到背侧脊髓,在那里它们被不同类别的感觉背侧中间神经元(dIs)处理。dIs 将感觉信息(如疼痛、热或痒)传递到大脑和/或运动回路,以引发适当的反应。它们还调节感觉信息的强度,是阿片类镇痛药的主要靶点。虽然指导腹侧和背侧细胞命运的发育机制被假设为相似的,但最近的研究表明,dI 命运是由新的机制决定的。在这篇综述中,我们将讨论指定脊髓背侧神经元模式的分子事件,从而产生不同的 dI 特性。然后,我们将讨论这种分子理解如何导致开发强大的干细胞方法来衍生多种脊髓细胞类型,包括 dIs,以及这些研究对治疗脊髓损伤和神经退行性疾病的意义。本文属于以下类别:神经疾病 > 干细胞和发育。