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In the present study, the hematopoietic site in oyster Crassostrea gigas was successfully identified in the proximal sector (designated G2\u2013G3) of the gill hinge with a substantial number of newborn cells and a minor presence of stem-like cells. The homologues of VEGF (CgVEGF) and its receptor CgVEGFR were characterized, and they interacted with each other. After the oysters received an injection of rCgVEGF, the number of EdU-positive (EdU+) cells increased within the G2\u2013G3 sector and the hemolymph. When the expression of CgVEGFR was inhibited by RNAi, the percentage of EdU+ cells in the hemolymph declined dramatically, but increased significantly in the G2\u2013G3 sector and EdU+ cells aggregated in this region. Meanwhile, the phosphorylation levels of CgErk and CgJNK, mRNA transcripts of cell proliferation-related and cell migration-related genes, reduced significantly. These results indicate that the proximal region of the hinge in gill was the site producing hemocytes, and CgVEGF-VEGFR-MAPK signaling pathway induced the migration of newborn hemocytes from this site to the circulating hemolymph, which provides new clues about hematopoiesis in primary invertebrates.<\/jats:p>","DOI":"10.3390\/cells14181446","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:31:41Z","timestamp":1758033101000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["VEGF-VEGFR Signaling Mechanism Directs the Migration of Newborn Hemocytes from the Hematopoietic Site of Oyster Crassostrea\u00a0gigas"],"prefix":"10.3390","volume":"14","author":[{"given":"Simiao","family":"Yu","sequence":"first","affiliation":[{"name":"Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian 116023, 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