Tryptophan hydroxylase Is Required for Eye Melanogenesis in the Planarian Schmidtea mediterranea

Melanins are ubiquitous and biologically important pigments, yet the molecular mechanisms that regulate their synthesis and biochemical composition are not fully understood. Here we present a study that supports a role for serotonin in melanin synthesis in the planarian Schmidtea mediterranea. We characterize the tryptophan hydroxylase (tph) gene, which encodes the rate-limiting enzyme in serotonin synthesis, and demonstrate by RNA interference that tph is essential for melanin production in the pigment cups of the planarian photoreceptors. We exploit this phenotype to investigate the biological function of pigment cups using a quantitative light-avoidance behavioral assay. Planarians lacking eye pigment remain phototactic, indicating that eye pigmentation is not essential for light avoidance in S. mediterranea, though it improves the efficiency of the photophobic response. Finally, we show that the eye pigmentation defect observed in tph knockdown animals can be rescued by injection of either the product of TPH, 5-hydroxytryptophan (5-HTP), or serotonin. Together, these results highlight a role for serotonin in melanogenesis, perhaps as a regulatory signal or as a pigment substrate. To our knowledge, this is the first example of this relationship to be reported outside of mammalian systems.黑色素是一类分布广泛且具有重要生物学意义的色素，但其合成调控与生化组成的分子机制尚未完全阐明。本研究针对地中海涡虫（Schmidtea mediterranea）展开，证实了5-羟色胺在其黑色素合成过程中发挥作用。我们对色氨酸羟化酶（tryptophan hydroxylase, TPH）基因进行了表征——该基因编码5-羟色胺合成的限速酶，并通过RNA干扰（RNA interference, RNAi）实验证实，TPH是涡虫感光细胞色素杯产生黑色素的必需基因。我们利用该表型，通过定量避光行为实验探究色素杯的生物学功能。结果显示，缺失眼部色素的涡虫仍具有趋光性，表明在S. mediterranea中，眼部色素沉着并非避光行为所必需，但可提升趋避光反应的效率。最后，我们发现：对TPH基因敲低的涡虫注射其催化产物5-羟色氨酸（5-hydroxytryptophan, 5-HTP）或5-羟色胺，均可挽救其眼部色素沉着缺陷。综上，本研究结果揭示了5-羟色胺在黑色素生成中的作用，其可能作为调控信号或色素底物参与该过程。据我们所知，这是首个在哺乳动物系统之外报道的此类关联案例。