Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
Dis Model Mech. 2018 Dec 12;11(12):dmm035097. doi: 10.1242/dmm.035097.
The neural crest (NC) is a transient population of embryonic progenitors that are implicated in a diverse range of congenital birth defects and pediatric syndromes. The broad spectrum of NC-related disorders can be attributed to the wide variety of differentiated cell types arising from the NC. models of NC development provide a powerful platform for testing the relative contributions of intrinsic and extrinsic factors mediating NC differentiation under normal and pathogenic conditions. Although differentiation is a dynamic process that unfolds over time, currently, there is no well-defined chronology that characterizes the progression of NC differentiation towards specific cell fates. In this study, we have optimized culture conditions for expansion of primary murine NC cells that give rise to both ectodermal and mesoectodermal derivatives, even after multiple passages. Significantly, we have delineated highly reproducible timelines that include distinct intermediate stages for lineage-specific NC differentiation In addition, isolating both cranial and trunk NC cells from the same embryos enabled us to make direct comparisons between the two cell populations over the course of differentiation. Our results define characteristic changes in cell morphology and behavior that track the temporal progression of NC cells as they differentiate along the neuronal, glial and chondrogenic lineages These benchmarks constitute a chronological baseline for assessing how genetic or environmental disruptions may facilitate or impede NC differentiation. Introducing a temporal dimension substantially increases the power of this platform for screening drugs or chemicals for developmental toxicity or therapeutic potential. This article has an associated First Person interview with the first author of the paper.
神经嵴(NC)是一种短暂存在的胚胎祖细胞群体,与多种先天性出生缺陷和儿科综合征有关。NC 相关疾病的广泛范围归因于 NC 产生的各种分化细胞类型。NC 发育模型为测试内在和外在因素在正常和病理条件下介导 NC 分化的相对贡献提供了一个强大的平台。尽管分化是一个随时间展开的动态过程,但目前还没有明确的时间顺序来描述 NC 分化为特定细胞命运的进展。在这项研究中,我们优化了培养条件,以扩增原代小鼠 NC 细胞,这些细胞可以产生外胚层和中胚层衍生物,即使经过多次传代也是如此。重要的是,我们划定了高度可重复的时间线,其中包括特定的中间阶段,用于 NC 分化的谱系特异性。此外,从同一胚胎中分离颅神经嵴和躯干神经嵴细胞,使我们能够在分化过程中直接比较这两个细胞群体。我们的研究结果定义了细胞形态和行为的特征变化,这些变化跟踪了 NC 细胞沿着神经元、神经胶质和软骨谱系分化的时间进展。这些基准构成了评估遗传或环境干扰如何促进或阻碍 NC 分化的时间基准。引入时间维度极大地提高了该平台筛选药物或化学物质的发育毒性或治疗潜力的能力。本文附有该论文第一作者的第一人称采访。