{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:33:06Z","timestamp":1793161986464,"version":"4.5.0"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["SP\/13\/5\/30288,FS\/15\/39\/31526,RG\/17\/7\/33217"],"award-info":[{"award-number":["SP\/13\/5\/30288,FS\/15\/39\/31526,RG\/17\/7\/33217"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MR\/P011543\/1"],"award-info":[{"award-number":["MR\/P011543\/1"]}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"crossref","award":["StGeorges-21\\2"],"award-info":[{"award-number":["StGeorges-21\\2"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"crossref"}]},{"name":"St George\u2019s Hospital Charity","award":["RES 20-21 003"],"award-info":[{"award-number":["RES 20-21 003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Pathogenic variants in kinesin\n                    <jats:italic>KIF11<\/jats:italic>\n                    underlie microcephaly-lymphedema-chorioretinopathy (MLC) syndrome. Although well known for regulating spindle dynamics ensuring successful cell division, the association of\n                    <jats:italic>KIF11<\/jats:italic>\n                    (encoding EG5) with development of the lymphatic system and how\n                    <jats:italic>KIF11<\/jats:italic>\n                    pathogenic variants lead to lymphatic dysfunction and lymphedema remain unknown. Using patient-derived lymphoblastoid cells, we demonstrated that patients with MLC carrying pathogenic stop-gain variants in\n                    <jats:italic>KIF11<\/jats:italic>\n                    have reduced mRNA and protein levels. Lymphoscintigraphy showed reduced tracer absorption, and intestinal lymphangiectasia was detected in one patient, pointing to impairment of lymphatic function caused by\n                    <jats:italic>KIF11<\/jats:italic>\n                    haploinsufficiency. We revealed that\n                    <jats:italic>KIF11<\/jats:italic>\n                    is expressed in early human and mouse development with the lymphatic markers VEGFR3, podoplanin, and PROX1. In zebrafish, single-cell RNA-Seq identified\n                    <jats:italic>kif11<\/jats:italic>\n                    specifically expressed in endothelial precursors. In human lymphatic endothelial cells, EG5 inhibition with ispinesib reduced VEGFC-driven AKT phosphorylation, migration, and spheroid sprouting.\n                    <jats:italic>KIF11<\/jats:italic>\n                    knockdown reduced\n                    <jats:italic>PROX1<\/jats:italic>\n                    and\n                    <jats:italic>VEGFR3<\/jats:italic>\n                    expression, providing for the first time to our knowledge a link between\n                    <jats:italic>KIF11<\/jats:italic>\n                    and drivers of lymphangiogenesis and lymphatic identity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.177656","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:26:02Z","timestamp":1766413562000},"source":"Crossref","is-referenced-by-count":6,"title":["Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective"],"prefix":"10.1172","volume":"11","author":[{"given":"Kazim","family":"Ogmen","sequence":"first","affiliation":[{"name":"School of Health & Medical Sciences, City St George\u2019s, University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Dobbins","sequence":"additional","affiliation":[{"name":"School of Health & Medical Sciences, City St George\u2019s, University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8503-3411","authenticated-orcid":true,"given":"Rose Yinghan","family":"Behncke","sequence":"additional","affiliation":[{"name":"Research Group Lymphovascular Medicine and Translational 3D-Histopathology, Institute of Medical and Human Genetics, Charit\u00e9 - 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