Hockman Dorit, Adameyko Igor, Kaucka Marketa, Barraud Perrine, Otani Tomoki, Hunt Adam, Hartwig Anna C, Sock Elisabeth, Waithe Dominic, Franck Marina C M, Ernfors Patrik, Ehinger Sean, Howard Marthe J, Brown Naoko, Reese Jeffrey, Baker Clare V H
Department of Physiology, Development and Neuroscience, University of Cambridge, Anatomy Building, Downing Street, Cambridge CB2 3DY, United Kingdom; Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DS, United Kingdom; Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden; Center for Brain Research, Medical University Vienna, 1090 Vienna, Austria.
Dev Biol. 2018 Dec 1;444 Suppl 1(Suppl 1):S308-S324. doi: 10.1016/j.ydbio.2018.05.016. Epub 2018 May 25.
Carotid body glomus cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific cells for Parkinson's disease therapy. Like adrenal chromaffin cells, which are also hypoxia-sensitive, glomus cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between glomus and adrenal chromaffin cell development. Moreover, histology has long suggested that glomus cell precursors are 'émigrés' from neighbouring ganglia/nerves, while multipotent nerve-associated glial cells are now known to make a significant contribution to the adrenal chromaffin cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to glomus cells. Finally, we resolve a paradox for the 'émigré' hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'émigrés' to the neural crest.
颈动脉体球细胞介导对动脉血缺氧的重要反射反应。它们是多巴胺能的，并分泌支持多巴胺能神经元的生长因子，这使得颈动脉体成为帕金森病治疗中患者特异性细胞的潜在来源。与同样对缺氧敏感的肾上腺嗜铬细胞一样，球细胞起源于神经嵴，需要转录因子Ascl1和Phox2b；否则，在分子水平上对它们的发育了解甚少。在这里，对鸡和小鼠的分析揭示了球细胞和肾上腺嗜铬细胞发育之间进一步显著的分子相似之处，尽管也存在一些差异。此外，长期以来组织学研究表明，球细胞前体是从邻近神经节/神经“迁移”而来的，而现在已知多能神经相关胶质细胞对小鼠肾上腺嗜铬细胞群体有重要贡献。我们展示了来自小鼠的条件性遗传谱系追踪数据，支持这样的假设，即表达胶质标志物蛋白脂质蛋白1的祖细胞，可能位于相邻神经节/神经中，也对球细胞有贡献。最后，我们解决了鸡的“迁移”假说中的一个矛盾——在鸡中，与颈动脉体最近的神经节是结状神经节，其中卫星胶质细胞起源于神经嵴，但神经元几乎完全起源于基板——通过将假定的结状神经元“迁移者”命运映射到神经嵴。
