Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA.
Development. 2012 Jan;139(1):179-90. doi: 10.1242/dev.071134. Epub 2011 Nov 24.
The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants.
脊髓包含多种在躯体感觉感知和运动控制中发挥特定作用的生理上不同的中间神经元细胞类型。然而，将多能脊髓祖细胞分化为这些特定中间神经元细胞类型的机制尚不清楚。在这项研究中，我们描述了一个受时间调控的转录程序，该程序控制着 Renshaw 细胞（RCs）的分化，RCs 是一种解剖学和功能上离散的脊髓中间神经元亚型。我们发现，在 V1 中间神经元神经发生的第一波中，Onecut 转录因子 Oc1 和 Oc2 的选择性激活是 RC 分化程序的关键步骤。RC 的发育还依赖于叉头转录因子 Foxd3，后者在有丝分裂后 V1 中间神经元中广泛表达。我们的研究表明，RCs 在一个狭窄的时间窗口中产生，并激活 Oc1 和 Oc2 的表达，这使我们假设，发育中的脊髓中的神经元多样性是由早期的空间和时间决定因素的综合作用建立的。
