{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:00:33Z","timestamp":1781820033468,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"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. Physiol."],"abstract":"<jats:p>SDF-1\/CXCR4 chemokine signaling are indispensable for cell migration, especially the Primordial Germ Cell (PGC) migration towards the gonadal ridge during early development. We earlier found that this signaling is largely conserved in the Japanese anchovy (<jats:italic>Engraulis japonicus<\/jats:italic>, EJ), and a mere treatment of CXCR4 antagonist, AMD3100, leads to germ cell depletion and thereafter gonad sterilization. However, the effect of AMD3100 was limited. So, in this research, we scouted for CXCR4 antagonist with higher potency by employing advanced artificial intelligence deep learning-based computer simulations. Three potential candidates, AMD3465, WZ811, and LY2510924, were selected and <jats:italic>in vivo<\/jats:italic> validation was conducted using Japanese anchovy embryos. We found that seven transmembrane motif of EJ CXCR4a and EJ CXCR4b were extremely similar with human homolog while the CXCR4 chemokine receptor N terminal (PF12109, essential for SDF-1 binding) was missing in EJ CXCR4b. 3D protein analysis and cavity search predicted the cavity in EJ CXCR4a to be five times larger (6,307\u00a0\u00c5\u00b3) than that in EJ CXCR4b (1,241\u00a0\u00c5\u00b3). Docking analysis demonstrated lower binding energy of AMD3100 and AMD3465 to EJ CXCR4a (Vina score \u22129.6) and EJ CXCR4b (Vina score \u22128.8), respectively. Furthermore, we observed significant PGC mismigration in microinjected AMD3465 treated groups at 10, 100 and 1 \u00d7 10<jats:sup>5<\/jats:sup>\u00a0nM concentration in 48\u00a0h post fertilized embryos. The other three antagonists showed various degrees of PGC dispersion, but no significant effect compared to their solvent control at tested concentrations was observed. Cumulatively, our results suggests that AMD3645 might be a better candidate for abnormal PGC migration in Japanese anchovy and warrants further investigation.<\/jats:p>","DOI":"10.3389\/fphys.2024.1349119","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T04:51:25Z","timestamp":1706849485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Modeling the SDF-1\/CXCR4 protein using advanced artificial intelligence and antagonist screening for Japanese anchovy"],"prefix":"10.3389","volume":"15","author":[{"given":"Issei","family":"Yahiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle Dominic Eguid","family":"Barnuevo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oga","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sipra","family":"Mohapatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiya","family":"Matsuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1741072","DOI":"10.1155\/2016\/1741072","article-title":"Primordial germ cells: current knowledge and perspectives","volume":"2016","author":"Aleksandar","year":"2016","journal-title":"Stem Cells Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0044-8486(89)90260-3","article-title":"Growth improvement in carp, Cyprinus carpio (Linnaeus), sterilized with 17\u03b1-methyltestosterone","volume":"76","author":"Ali","year":"1989","journal-title":"Aquaculture"},{"key":"B3","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.stemcr.2019.07.013","article-title":"Estrogen receptor \u03b22 oversees germ cell maintenance and gonadal sex differentiation in medaka, Oryzias latipes","volume":"13","author":"Chakraborty","year":"2019","journal-title":"Stem Cell Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6996","DOI":"10.1093\/emboj\/16.23.6996","article-title":"Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1","volume":"16","author":"Crump","year":"1997","journal-title":"EMBO J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1471-213X-7-23","article-title":"Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7\/RDC1","volume":"7","author":"Dambly-Chaudi\u00e8re","year":"2007","journal-title":"BMC Dev. 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