Taroc Ed Zandro M, Amato Enrico, Semon Alexis M, Dolphin Nikki, Beck Briane, Belin Sophie, Poitelon Yannick, Forni Paolo E
Department of Biological Sciences, The Center for Neuroscience Research, the RNA Institute, University at Albany, State University of New York, Albany, New York, USA.
National Institute of Dental and Craniofacial Research, Intramural Research Program, Neural Crest Development and Disease Unit, National Institutes of Health, Bethesda, Maryland, USA.
Glia. 2025 Jul 9. doi: 10.1002/glia.70057.
Olfactory Ensheathing Cells (OECs) are glial cells originating from the neural crest and are critical for bundling olfactory axons to the brain. Their development is crucial for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs have garnered interest as potential therapeutic targets for central nervous system lesions, although their development is not fully understood. Our single-cell RNA sequencing of mouse embryonic nasal tissues suggests that OECs and Schwann cells share a common origin from Schwann cell precursors yet exhibit significant genetic differences. The transcription factors Yap and Taz have previously been shown to play a crucial role in Schwann cell development. We used Sox10-Cre mice to conditionally ablate Yap and Taz in the migrating neural crest and its derivatives. Our analyses showed reduced Sox10+ glial cells along nerves in the nasal region, altered gene expression in Schwann cells (SCs), melanocytes, and OECs, and a significant reduction in olfactory sensory neurons and vascularization in the vomeronasal organ. However, despite these changes, GnRH-1 neuronal migration remained unaffected. Our findings highlight the importance of the Hippo pathway in OEC development and how changes in cranial neural crest derivatives indirectly impact the development of olfactory epithelia.
嗅鞘细胞(OECs)是源自神经嵴的神经胶质细胞,对于将嗅觉轴突束集到大脑至关重要。它们的发育对于促性腺激素释放激素-1(GnRH-1)神经元的迁移至关重要,而GnRH-1神经元对青春期和生育能力至关重要。尽管对其发育尚未完全了解,但OECs作为中枢神经系统损伤的潜在治疗靶点已引起关注。我们对小鼠胚胎鼻组织进行的单细胞RNA测序表明,OECs和雪旺细胞源自雪旺细胞前体的共同起源,但表现出显著的基因差异。转录因子Yap和Taz先前已被证明在雪旺细胞发育中起关键作用。我们使用Sox10-Cre小鼠有条件地在迁移的神经嵴及其衍生物中敲除Yap和Taz。我们的分析显示,鼻区域神经沿线的Sox10+神经胶质细胞减少,雪旺细胞(SCs)、黑素细胞和OECs中的基因表达改变,犁鼻器中的嗅觉感觉神经元和血管化显著减少。然而,尽管发生了这些变化,GnRH-1神经元的迁移仍然不受影响。我们的研究结果突出了Hippo信号通路在OEC发育中的重要性,以及颅神经嵴衍生物的变化如何间接影响嗅觉上皮的发育。