Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715.
Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53715.
Proc Natl Acad Sci U S A. 2024 Jun 25;121(26):e2321349121. doi: 10.1073/pnas.2321349121. Epub 2024 Jun 18.
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 (). Inhibiting 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 and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after or 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.
生殖细胞受局部微环境（龛）调控，龛分泌有指导意义的线索。保守的发育信号分子作为龛衍生的调节因子发挥作用，但其他类型的龛信号仍有待确定。性涡虫的单细胞 RNA 测序显示龛细胞表达非核糖体肽合成酶 ()。抑制 导致雌性生殖器官丧失和睾丸增生。质谱检测到二肽 β-丙氨酰-色胺（BATT），它与生殖系统的发育有关，并且需要 和单胺递质合成酶芳香族 L-氨基酸脱羧酶（AADC）才能产生。外源性 BATT 可挽救 或 抑制后的生殖缺陷，恢复生育能力。因此，龛细胞提供的非核糖体单胺衍生肽作为关键信号触发涡虫生殖发育。这些发现揭示了单胺在龛-生殖细胞信号中的意想不到的作用。此外，鉴于最近报道的 BATT 作为一种雄性衍生因子在雌性血吸虫生殖成熟中的作用，这些结果对寄生扁形动物的进化具有重要意义，并表明非核糖体肽作为其他生物体中信号分子的潜在作用。
