PDF(Pubmed)
Abstract：
Germ cells are regulated by local microenvironments (niches), which secrete instructive cues. Conserved developmental signaling molecules act as niche-derived regulatory factors, yet other types of niche signals remain to be identified. Single-cell RNA-sequencing of sexual planarians revealed niche cells expressing a nonribosomal peptide synthetase (nrps). Inhibiting nrps led to loss of female reproductive organs and testis hyperplasia. Mass spectrometry detected the dipeptide β-alanyl-tryptamine (BATT), which is associated with reproductive system development and requires nrps and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after nrps or aadc inhibition, restoring fertility. Thus, a nonribosomal, monoamine-derived peptide provided by niche cells acts as a critical signal to trigger planarian reproductive development. These findings reveal an unexpected function for monoamines in niche-germ cell signaling. Furthermore, given the recently reported role for BATT as a male-derived factor required for reproductive maturation of female schistosomes, these results have important implications for the evolution of parasitic flatworms and suggest a potential role for nonribosomal peptides as signaling molecules in other organisms.
摘要：
生殖细胞受局部微环境（壁龛）的调节，分泌有启发性的线索。保守的发育信号分子充当生态位衍生的调节因子，然而，其他类型的生态位信号仍有待识别。有性涡虫的单细胞RNA测序显示，小生境细胞表达非核糖体肽合成酶（nrps）。抑制nrps导致女性生殖器官丧失和睾丸增生。质谱检测二肽β-丙氨酰-色胺(BATT),与生殖系统发育有关，需要nrps和单胺递质合成酶芳香族L-氨基酸脱羧酶（AADC）来生产。外源性BATT在nrps或aadc抑制后拯救了生殖缺陷，恢复生育能力。因此，非核糖体，小生境细胞提供的单胺衍生肽是触发涡虫生殖发育的关键信号。这些发现揭示了单胺在小生境生殖细胞信号传导中的意想不到的功能。此外，鉴于最近报道的BATT作为女性血吸虫生殖成熟所需的男性衍生因子的作用，这些结果对寄生扁虫的进化具有重要意义，并表明非核糖体肽在其他生物中作为信号分子的潜在作用。
