{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:26:40Z","timestamp":1791084400419,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,22]],"date-time":"2013-01-22T00:00:00Z","timestamp":1358812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:styled-content>Background:<\/jats:styled-content> Histone deacetylases (HDACs) regulate multiple developmental processes and cellular functions. However, their roles in blood development have not been determined, and in <jats:italic>Xenopus laevis<\/jats:italic> a specific function for HDACs has yet to be identified. Here, we employed the class I selective HDAC inhibitor, valproic acid (VPA), to show that HDAC activity is required for primitive hematopoiesis. <jats:styled-content>Results:<\/jats:styled-content> VPA treatment during gastrulation resulted in a complete absence of red blood cells (RBCs) in <jats:italic>Xenopus<\/jats:italic> tadpoles, but did not affect development of other mesodermal tissues, including myeloid and endothelial lineages. These effects of VPA were mimicked by Trichostatin A (TSA), a well\u2010established pan\u2010HDAC inhibitor, but not by valpromide, which is structurally similar to VPA but does not inhibit HDACs. VPA also caused a marked, dose\u2010dependent loss of primitive erythroid progenitors in mouse yolk sac explants at clinically relevant concentrations. In addition, VPA treatment inhibited erythropoietic development downstream of <jats:italic>bmp4<\/jats:italic> and <jats:italic>gata1<\/jats:italic> in <jats:italic>Xenopus<\/jats:italic> ectodermal explants. <jats:styled-content>Conclusions:<\/jats:styled-content> These findings suggest an important role for class I HDACs in primitive hematopoiesis. Our work also demonstrates that specific developmental defects associated with exposure to VPA, a significant teratogen in humans, arise through inhibition of class I HDACs. <jats:italic>Developmental Dynamics 242:108\u2013121, 2013<\/jats:italic>. \u00a9 2012 Wiley Periodicals,Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.23906","type":"journal-article","created":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T06:37:15Z","timestamp":1353998235000},"page":"108-121","source":"Crossref","is-referenced-by-count":10,"title":["Regulation of Primitive Hematopoiesis by Class I Histone Deacetylases"],"prefix":"10.1002","volume":"242","author":[{"given":"Rishita R.","family":"Shah","sequence":"first","affiliation":[{"name":"Cell and Molecular Biology Graduate Group University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Koniski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Center for Pediatric Biomedical Research University of Rochester Medical Center Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Shinde","sequence":"additional","affiliation":[{"name":"Pharmacology Graduate Group University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby A.","family":"Blythe","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Graduate Group University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Fass","sequence":"additional","affiliation":[{"name":"Stanley Center for Psychiatric Research Broad Institute of Harvard and MIT Cambridge Massachusetts"},{"name":"Center for Human Genetic Research Massachusetts General Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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