Serotonergic neuroepithelial cells (NECs) in larval zebrafish are believed to be O₂ chemoreceptors. Serotonin (5-HT) within these NECs has been implicated as a neurotransmitter mediating the hypoxic ventilatory response (HVR). Here, we use knockout approaches to discern the role of 5-HT in regulating the HVR by targeting the rate limiting enzyme for 5-HT synthesis, tryptophan hydroxylase (Tph). Using transgenic lines, we determined that Tph1a is expressed in skin and pharyngeal arch NECs, as well as in pharyngeal arch Merkel-like cells (MLCs), whereas Tph1b is expressed predominately in MLCs. Knocking out the two tph1 paralogs resulted in similar changes in detectable serotonergic cell density between the two mutants, yet their responses to hypoxia (35 mmHg) were different. Larvae lacking Tph1a (tph1a^−/− mutants) displayed a higher ventilation rate when exposed to hypoxia compared to wild-types, whereas tph1b^−/− mutants exhibited a lower ventilation rate suggesting that 5-HT located in locations other than NECs, may play a dominant role in regulating the HVR.

斑马鱼幼虫中的血清素神经上皮细胞 (NEC) 被认为是 O ₂化学感受器。这些 NEC 中的血清素 (5-HT) 被认为是介导缺氧通气反应 (HVR) 的神经递质。在这里，我们使用敲除方法通过靶向 5-HT 合成的限速酶色氨酸羟化酶 (Tph) 来识别 5-HT 在调节 HVR 中的作用。使用转基因系，我们确定 Tph1a 在皮肤和咽弓 NEC 以及咽弓默克尔样细胞 (MLC) 中表达，而 Tph1b 主要在 MLC 中表达。敲掉两个tph1paralogs 导致两个突变体之间可检测的血清素细胞密度发生类似变化，但它们对缺氧 (35 mmHg) 的反应不同。与野生型相比，缺乏 Tph1a 的幼虫（tph1a ^-/-突变体）在暴露于缺氧时表现出更高的通气率，而tph1b ^-/-突变体表现出较低的通气率，表明位于 NEC 以外的位置的 5-HT 可能发挥作用在调节 HVR 中起主导作用。