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Thymus hypoplasia reduces peripheral T cell numbers, leading to more frequent infections. We report that embryonic hypoplastic thymuses from mouse models of 22q11.2DS (Tbx1neo2\/neo2) have distinct mesenchymal cell subsets, including an expansion of Sox9+ chondrocytes. Chondrocytes produce collagens and extracellular matrix (ECM) proteins, which can affect thymus size and vascularization. Two compounds, minoxidil and PGE2, restored growth for Tbx1neo2\/neo2 embryonic thymuses when administered to pregnant mice prior to formation of the thymic anlage. The dysregulation of the mesenchymal and endothelial transcriptomes was corrected with minoxidil in Tbx1neo2\/neo2 thymuses. This was confirmed by the diminished expression of Sox9-driven type II, IX, and XI cartilaginous collagens and other ECM proteins. Furthermore, the location of parathyroids was corrected in Tbx1neo2\/neo2 embryos. In summary, these findings reveal that targeting prenatal mesenchymal differentiation can correct multiple congenital anomalies in mouse models of 22q11.2DS.<\/jats:p>","DOI":"10.70962\/jhi.20250143","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T06:21:16Z","timestamp":1752301276000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Minoxidil restores thymic growth in 22q11.2 deletion syndrome by limiting Sox9+ chondrocyte expansion"],"prefix":"10.70962","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-996X","authenticated-orcid":true,"given":"Pratibha","family":"Bhalla","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Texas Southwestern Medical Center 1 Department of Immunology, , Dallas, 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