Steinacher Claudia, Nishio Shin-Ya, Usami Shin-Ichi, Dudas Jozsef, Rieder Dietmar, Rask-Andersen Helge, Crespo Berta, Moreno Nadjeda, Konschake Marko, Seifarth Christof, Glueckert Rudolf
Department of Otorhinolaryngology, Medical University Innsbruck, 6020 Innsbruck, Austria.
Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 3-1-1 Asahi, Nagano 390-8621, Japan.
Int J Mol Sci. 2024 Dec 3;25(23):13007. doi: 10.3390/ijms252313007.
We determined the relative expression levels of the receptors , , , and and ligands , , , and with RNAseq analysis on fetal human inner ear samples, located TrkB and TrkC proteins, and quantified with in situ hybridization on histological sections between gestational weeks (GW) 9 to 19. Spiral ganglion neurons (SGNs) and satellite glia appear to be the main source of and synthesis peaks twice at GW10 and GW15-GW17. Tonotopical gradients of revert between GW8 and GW15 and follow a maturation and innervation density gradient in SGNs. follows the same time course of expression as . Immunostaining reveals that TrkB signaling may act mainly through satellite glia, Schwann cells, and supporting cells of Kölliker's organ, while TrkC signaling targets SGNs and pillar cells in humans. The expression is upregulated when is downregulated, suggesting a balancing effect for sustained TrkB activation during fetal development. The mission of neurotrophins expects nerve fiber guidance, innervation, maturation, and trophic effects. The data shall serve to provide a better understanding of neurotrophic regulation and action in human development and to assess the transferability of neurotrophic regenerative therapy from animal models.
我们通过对人类胎儿内耳样本进行RNA测序分析，确定了受体、、、以及配体、、、的相对表达水平，定位了TrkB和TrkC蛋白，并在妊娠第9至19周的组织切片上通过原位杂交对进行了定量分析。螺旋神经节神经元（SGNs）和卫星神经胶质细胞似乎是的主要来源，且在妊娠第10周以及第15至17周时合成出现两次高峰。的音频拓扑梯度在妊娠第8周和第15周之间发生逆转，并遵循SGNs中的成熟和神经支配密度梯度。的表达与的时间进程相同。免疫染色显示，TrkB信号传导可能主要通过卫星神经胶质细胞、施万细胞以及柯蒂氏器的支持细胞起作用，而TrkC信号传导在人类中的作用靶点是SGNs和柱状细胞。当被下调时，的表达会上调，这表明在胎儿发育过程中对持续的TrkB激活具有平衡作用。神经营养因子的作用包括神经纤维导向、神经支配、成熟和营养作用。这些数据将有助于更好地理解人类发育过程中的神经营养调节和作用，并评估神经营养再生疗法从动物模型的可转移性。
