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They can be found in most organs of the body, where they also contribute to normal tissue functioning, for example by engaging in crosstalk with nerves. Despite this, they are most widely known for their detrimental roles in allergy, anaphylaxis, and atopic disease. Just like macrophages, mast cells were conventionally thought to originate from the bone marrow. However, they are already present in fetal tissues before the onset of bone marrow hematopoiesis, questioning this dogma. In recent years, our view of myeloid cell ontogeny has been revised. We now know that the first mast cells originate from progenitors made in the extra\u2010embryonic yolk sac, and later get supplemented with mast cells produced from subsequent waves of hematopoiesis. In most connective tissues, sizeable populations of fetal\u2010derived mast cells persist into adulthood, where they self\u2010maintain largely independently from the bone marrow. These developmental origins are highly reminiscent of macrophages, which are known to have critical functions in development. Mast cells too may thus support healthy development. Their fetal origins and longevity also make mast cells susceptible to genetic and environmental perturbations, which may render them pathological. Here, we review our current understanding of mast cell biology from a developmental perspective. We first summarize how mast cell populations are established from distinct hematopoietic progenitor waves, and how they are subsequently maintained throughout life. We then discuss what functions mast cells may normally have at early life stages, and how they may be co\u2010opted to cause, worsen, or increase susceptibility to disease.<\/jats:p>","DOI":"10.1111\/imr.13191","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T10:19:12Z","timestamp":1675851552000},"page":"31-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Mast cell ontogeny: From fetal development to life\u2010long health and disease"],"prefix":"10.1111","volume":"315","author":[{"given":"Shin Li","family":"Chia","sequence":"first","affiliation":[{"name":"Institute for Regeneration and Repair, Centre for Inflammation Research &amp; Centre for Reproductive Health The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simran","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Institute for Regeneration and 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