{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:28:03Z","timestamp":1789730883310,"version":"4.0.1"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 043403"],"award-info":[{"award-number":["R01 043403"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI150776"],"award-info":[{"award-number":["R01 AI150776"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-1948-20240404"],"award-info":[{"award-number":["I-1948-20240404"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["Investigator Award"],"award-info":[{"award-number":["Investigator Award"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:p>\n                    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 (\n                    <jats:italic>nrps<\/jats:italic>\n                    ). Inhibiting\n                    <jats:italic>nrps<\/jats:italic>\n                    led to loss of female reproductive organs and testis hyperplasia. Mass spectrometry detected the dipeptide \u03b2-alanyl-tryptamine (BATT), which is associated with reproductive system development and requires\n                    <jats:italic>nrps<\/jats:italic>\n                    and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after\n                    <jats:italic>nrps<\/jats:italic>\n                    or\n                    <jats:italic>aadc<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2321349121","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T13:25:32Z","timestamp":1718717132000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["A niche-derived nonribosomal peptide triggers planarian sexual development"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-8389","authenticated-orcid":false,"given":"Melanie","family":"Issigonis","sequence":"first","affiliation":[{"name":"Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715"},{"name":"Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53715"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Browder","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53715"},{"name":"HHMI, University of Wisconsin-Madison, Madison, WI 53715"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5237-1004","authenticated-orcid":false,"suffix":"III","given":"James J.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0793-022X","authenticated-orcid":false,"given":"Phillip A.","family":"Newmark","sequence":"additional","affiliation":[{"name":"Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715"},{"name":"Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53715"},{"name":"HHMI, University of Wisconsin-Madison, Madison, WI 53715"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"e_1_3_5_1_2","first-page":"309","volume-title":"Handbook of Behavioral Neuroscience","author":"Whitaker-Azmitia P. 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