{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:16:50Z","timestamp":1790777810962,"version":"4.1.0"},"reference-count":73,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks\/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks\/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1\u2013induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.<\/jats:p>","DOI":"10.1182\/blood.2020010310","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T02:03:30Z","timestamp":1614045810000},"page":"2756-2769","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-2438","authenticated-orcid":false,"given":"Christopher","family":"Hoover","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"},{"name":"Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kondo","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojing","family":"Shao","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"McDaniel","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-0593","authenticated-orcid":false,"given":"Robert","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics\u2013UNC Blood Research 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