{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T07:09:48Z","timestamp":1771571388996,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Alveolar echinococcosis (AE), a neglected zoonotic disease, is caused by the infiltrative growth of the metacestode larval stage of the cestode\n                    <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                    within host organs. We previously showed that metacestode development relies on the mitotic activity of a population of parasite stem cells known as germinative cells. However, the molecular mechanisms that control\n                    <jats:italic>Echinococcus<\/jats:italic>\n                    stem cell dynamics such as cell-cycle progression, self-renewal, and differentiation remain poorly understood. Building on earlier reports implicating epidermal growth factor (EGF) signalling in stem cell regulation, we here characterize the parasite\u2019s repertoire of three EGF receptors. Using RNAi and inhibitor assays, we identify one receptor, EmER1, as essential for the formation of metacestode vesicles from germinative cells. We further demonstrate that EmER1 is targeted by afatinib, an EGF receptor inhibitor with potent anti-parasitic activity both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Through bioinformatic analyses and membrane-bound yeast two-hybrid assays, we identified a parasite-derived, neuregulin-like ligand for EmER1, termed EmNRG, whose expression is strongly upregulated in metacestode vesicles during clonal expansion of germinative cells. RNAi-mediated knockdown of the EmNRG encoding gene severely impaired the capacity of germinative cells to generate metacestode vesicles. Our data support that EmNRG and EmER1 constitute a cognate ligand - receptor system regulating the balance between asymmetric and symmetric stem cell division in\n                    <jats:italic>E. multilocularis<\/jats:italic>\n                    . These findings provide new insights into\n                    <jats:italic>Echinococcus<\/jats:italic>\n                    stem cell biology and highlight EGF signalling as a promising avenue for developing novel anti-echinococcosis therapeutics.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1742233","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:42:15Z","timestamp":1771569735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A neuregulin-like ligand and EGF receptor underpin Echinococcus multilocularis development"],"prefix":"10.3389","volume":"16","author":[{"given":"Akito","family":"Koike","sequence":"first","affiliation":[{"name":"Consultant Laboratory for Echinococcosis, Institute of Hygiene and Microbiology, University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Consultant Laboratory for Echinococcosis, Institute of Hygiene and Microbiology, University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Cailliau","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, UMR 8576-UGSF-Unit\u00e9 de Glycobiologie Structurale et Fonctionnelle","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"Vicogne","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Becker","sequence":"additional","affiliation":[{"name":"Intana Bioscience GmbH","place":["Martinsried, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette","family":"Dissous","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Hannus","sequence":"additional","affiliation":[{"name":"Intana Bioscience GmbH","place":["Martinsried, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Brehm","sequence":"additional","affiliation":[{"name":"Consultant Laboratory for Echinococcosis, Institute of Hygiene and Microbiology, University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28071","article-title":"Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea","volume":"6","author":"Barberan","year":"2016","journal-title":"Sci. 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