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Sex effects can be the result of sex chromosome complement (XX vs. XY) and\/or gonadal hormone influence. The contributions of each can be separated using the four-core genotype mouse model (FCG), where sex chromosome complement and gonadal sex are decoupled. While studies of FCG mice have evaluated brain differences in adulthood, it is still unclear how sex chromosome and sex hormone effects emerge through development in both healthy and pathological contexts. Our study utilizes longitudinal MRI with the FCG model to investigate sex effects in healthy development and after CRT in wildtype and immune-modified\n                    <jats:italic>Ccl2<\/jats:italic>\n                    -knockout mice. Our findings in normally developing mice reveal a relatively prominent chromosome effect prepubertally, compared to sex hormone effects which largely emerge later. Spatially, sex chromosome and hormone influences were independent of one another. After CRT in\n                    <jats:italic>Ccl2<\/jats:italic>\n                    -knockout mice, both male chromosomes and male hormones similarly improved brain outcomes but did so more separately than in combination. Our findings highlight the crucial role of sex chromosomes in early development and identify roles for sex chromosomes and hormones after CRT-induced inflammation, highlighting the influences of biological sex in both normal brain development and pathology.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2404042121","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:18:46Z","timestamp":1724930326000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-2875","authenticated-orcid":false,"given":"Jonas","family":"Yeung","sequence":"first","affiliation":[{"name":"Mouse Imaging Centre, Hospital for Sick Children, Toronto ON M5T 3H7, Canada"},{"name":"Translational Medicine, Hospital for Sick Children, Toronto ON M5G 1X8, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7324-0541","authenticated-orcid":false,"given":"Taylor","family":"DeYoung","sequence":"additional","affiliation":[{"name":"Mouse Imaging Centre, Hospital for Sick Children, Toronto ON M5T 3H7, Canada"},{"name":"Translational Medicine, Hospital for Sick Children, Toronto ON M5G 1X8, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-5552","authenticated-orcid":false,"given":"Shoshana","family":"Spring","sequence":"additional","affiliation":[{"name":"Mouse Imaging Centre, Hospital for Sick Children, Toronto ON M5T 3H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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