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In mammals, it is generally believed that DCs originate exclusively from hematopoietic stem cells (HSCs). Using a temporal-spatial resolved fate-mapping system, here we show that, in zebrafish, DCs arise from two sources: dorsal aorta-born endothelium-derived hematopoietic progenitors (EHPs) and HSCs. The EHP-derived DCs emerge early, predominantly colonizing the developing thymus during larval stages and diminishing by juvenile stages. In contrast, HSC-derived DCs emerge later and can populate different tissues from late larval stages to adulthood. We further document that the EHP- and HSC-derived DCs display different dependencies on Fms-like tyrosine kinase 3 (Flt3), a pivotal receptor tyrosine kinase crucial for DC development in mammals. Our study reveals the presence of two distinct waves of DC development in zebrafish, each with unique origins and developmental controls.<\/jats:p>","DOI":"10.1242\/dev.204410","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T09:43:44Z","timestamp":1737971024000},"source":"Crossref","is-referenced-by-count":2,"title":["Dendritic cells in developing and adult zebrafish arise from different origins and display distinct <i>flt3<\/i> dependencies"],"prefix":"10.1242","volume":"152","author":[{"given":"Guanzhen","family":"Lin","sequence":"first","affiliation":[{"name":"School of Life Sciences, Southern University of Science and Technology 1 Department of Immunology and Microbiology , , Shenzhen 518055 ,","place":["China"]},{"name":"the Hong Kong University of Science and Technology, Clear Water Bay 2 Division of Life Science , , Hong Kong 000000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Southern University of Science and Technology 1 Department of Immunology and Microbiology , , Shenzhen 518055 ,","place":["China"]},{"name":"the Hong Kong University of Science and Technology, Clear Water Bay 2 Division of Life Science , , Hong Kong 000000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Giang","family":"Pham","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Southern University of Science and Technology 1 Department of Immunology and Microbiology , , Shenzhen 518055 ,","place":["China"]},{"name":"the Hong Kong University of Science and Technology, Clear Water Bay 2 Division of Life Science , , Hong Kong 000000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-7682","authenticated-orcid":false,"given":"Zilong","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Southern University of Science and Technology 1 Department of Immunology and Microbiology , , Shenzhen 518055 ,","place":["China"]},{"name":"3 Shenzhen Bay Laboratory, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"2025021711371041700_DEV204410C1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.stem.2013.08.012","article-title":"Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells","volume":"13","author":"B\u00f6iers","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2025021711371041700_DEV204410C2","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1146\/annurev-immunol-061020-053707","article-title":"Dendritic cells revisited","volume":"39","author":"Cabeza-Cabrerizo","year":"2021","journal-title":"Annu. 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