{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Issigonis M"],"funding":["Welch Foundation (The Welch Foundation)","NICHD NIH HHS","Howard Hughes Medical Institute","NIAID NIH HHS","HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)","HHS | NIH | National Institute of Allergy and Infectious Diseases","Welch Foundation","Howard Hughes Medical Institute (HHMI)"],"pagination":["e2321349121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11214079"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(26)"],"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 (<i>nrps</i>). Inhibiting <i>nrps</i> 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 <i>nrps</i> and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after <i>nrps</i> or <i>aadc</i> 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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["A niche-derived nonribosomal peptide triggers planarian sexual development."],"pmcid":["PMC11214079"],"funding_grant_id":["I-1948-20240404","R01 AI150776","Investigator Award","R01 043403","R01 HD043403"],"pubmed_authors":["Browder KL","Issigonis M","Newmark PA","Collins JJ","Chen R"],"additional_accession":[]},"is_claimable":false,"name":"A niche-derived nonribosomal peptide triggers planarian sexual development.","description":"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 (<i>nrps</i>). Inhibiting <i>nrps</i> 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 <i>nrps</i> and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after <i>nrps</i> or <i>aadc</i> 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-03-27T16:09:03.49Z","creation":"2025-08-30T03:05:37.393Z"},"accession":"S-EPMC11214079","cross_references":{"pubmed":["38889152"],"doi":["10.1073/pnas.2321349121"]}}