Maintenance and regeneration of the zebrafish olfactory epithelium (OE) are supported by two distinct progenitor cell populations that occupy spatially discrete stem cell niches and respond to different tissue conditions. Globose basal cells (GBCs) reside at the inner and peripheral margins of the sensory OE and are constitutively active to replace sporadically dying olfactory sensory neurons (OSNs). In contrast, horizontal basal cells (HBCs) are uniformly distributed across the sensory tissue and are selectively activated by acute injury conditions. Here we show that expression of the heparin-binding epidermal growth factor-like growth factor (HB-EGF) is strongly and transiently upregulated in response to OE injury and signals through the EGF receptor (EGFR), which is expressed by HBCs. Exogenous stimulation of the OE with recombinant HB-EGF promotes HBC expansion and OSN neurogenesis in a pattern that resembles the tissue response to injury. In contrast, pharmacological inhibition of HB-EGF membrane shedding, HB-EGF availability, and EGFR signaling strongly attenuate or delay injury-induced HBC activity and OSN restoration without affecting maintenance neurogenesis by GBCs. Thus, HB-EGF/EGFR signaling appears to be a critical component of the signaling network that controls HBC activity and, consequently, repair neurogenesis in the zebrafish OE.

中文翻译：

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HB-EGF促进斑马鱼嗅上皮祖细胞增殖和感觉神经元再生

斑马鱼嗅上皮（OE）的维持和再生由两种不同的祖细胞群支持，它们占据空间上离散的干细胞生态位并对不同的组织条件做出反应。球形基底细胞 (GBC) 位于感觉 OE 的内部和外周边缘，并且具有组成性活性，可以替代零星死亡的嗅觉感觉神经元 (OSN)。相比之下，水平基底细胞（HBC）均匀分布在感觉组织中，并在急性损伤条件下选择性激活。在这里，我们发现，肝素结合表皮生长因子样生长因子 (HB-EGF) 的表达在 OE 损伤和通过 EGF 受体 (EGFR)（由 HBC 表达）的信号的响应下强烈且短暂地上调。用重组 HB-EGF 对 OE 进行外源刺激可促进 HBC 扩增和 OSN 神经发生，其模式类似于组织对损伤的反应。相反，对 HB-EGF 膜脱落、HB-EGF 可用性和 EGFR 信号传导的药理学抑制会强烈减弱或延迟损伤诱导的 HBC 活性和 OSN 恢复，而不影响 GBC 的维持性神经发生。因此，HB-EGF/EGFR 信号传导似乎是控制 HBC 活性的信号传导网络的关键组成部分，从而修复斑马鱼 OE 中的神经发生。