Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Chem Senses. 2020 May 29;45(5):333-346. doi: 10.1093/chemse/bjaa027.
Both canonical olfactory sensory neurons (OSNs) and sensory neurons belonging to the guanylate cyclase D (GCD) "necklace" subsystem are housed in the main olfactory epithelium, which is continuously bombarded by toxins, pathogens, and debris from the outside world. Canonical OSNs address this challenge, in part, by undergoing renewal through neurogenesis; however, it is not clear whether GCD OSNs also continuously regenerate and, if so, whether newborn GCD precursors follow a similar developmental trajectory to that taken by canonical OSNs. Here, we demonstrate that GCD OSNs are born throughout adulthood and can persist in the epithelium for several months. Phosphodiesterase 2A is upregulated early in the differentiation process, followed by the sequential downregulation of β-tubulin and the upregulation of CART protein. The GCD and MS4A receptors that confer sensory responses upon GCD neurons are initially expressed midway through this process but become most highly expressed once CART levels are maximal late in GCD OSN development. GCD OSN maturation is accompanied by a horizontal migration of neurons toward the central, curved portions of the cul-de-sac regions where necklace cells are concentrated. These findings demonstrate that-like their canonical counterparts-GCD OSNs undergo continuous renewal and define a GCD-specific developmental trajectory linking neurogenesis, maturation, and migration.
经典嗅觉感觉神经元 (OSN) 和属于鸟苷酸环化酶 D (GCD)“项链”亚系的感觉神经元都位于主嗅觉上皮中，该上皮不断受到来自外界的毒素、病原体和碎片的侵袭。经典 OSN 通过神经发生来应对这一挑战；然而，目前尚不清楚 GCD OSN 是否也在持续再生，如果是，新生的 GCD 前体细胞是否遵循与经典 OSN 相似的发育轨迹。在这里，我们证明 GCD OSN 在整个成年期都会产生，并能在上皮中持续存在数月。磷酸二酯酶 2A 在分化过程的早期上调，随后β-微管蛋白的顺序下调和 CART 蛋白的上调。赋予 GCD 神经元感觉反应的 GCD 和 MS4A 受体在这个过程的中途开始表达，但一旦 CART 水平在 GCD OSN 发育的后期达到最大值，表达水平就会达到最高。GCD OSN 的成熟伴随着神经元向中央、弯曲的壶腹区域的水平迁移，项链细胞集中在这些区域。这些发现表明，与经典的 OSN 一样，GCD OSN 经历了持续的更新，并定义了一个 GCD 特异性的发育轨迹，将神经发生、成熟和迁移联系起来。
