{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:10:07Z","timestamp":1783930207282,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"De Snoo\u2013van \u2019t Hoogerhuijs Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cerebrovascular disorders, encompassing conditions such as stroke, aneurysms, and arteriovenous malformations, are often associated with developmental malformations of the intracranial arterial system, including the circle of Willis. The circle of Willis plays a crucial role in establishing a collateral vascular network essential for ensuring adequate cerebral blood supply. However, the intricate process of human intracranial vascular development, known as vascular neuroembryology, remains complex and incompletely understood. The diverse array of anatomical vascular variations observed in clinical practice is a direct outcome of this developmental process. We present a chronological overview of human neurovascular embryology using stage-resolved three-dimensional reconstructions of the developing intracranial arterial system. Histological sections of 26 human embryos ranging from Carnegie stages (CS) 11 to 23 were digitally reconstructed and manually segmented in Amira software (versions 5.3\u20135.6; Thermo Fisher Scientific, Waltham, MA, USA) to generate detailed 3D models of the cranial vasculature and adjacent anatomical structures, including the neural tube, cranial nerves, eye, and ear. Sequential 3D reconstruction revealed progressive remodeling of the primitive cranial vasculature and key developmental transitions underlying formation of the circle of Willis. By integrating these developmental observations with existing embryological literature, we refine current models of neurovascular development, with particular emphasis on the ophthalmic and trigeminal arterial systems. These findings provide an updated developmental framework for interpreting normal and variant intracranial vascular anatomy encountered in clinical practice.<\/jats:p>","DOI":"10.3390\/life16071153","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"1153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vascular Neuroembryology: The Genesis of the Intracranial Arterial System and the Circle of Willis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-9370","authenticated-orcid":false,"given":"Karl","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Oral Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081 LA  Amsterdam, The Netherlands"},{"name":"Department of Medical Biology, Section Clinical Anatomy & Embryology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ  Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9758-3278","authenticated-orcid":false,"given":"Chelsey Marjana","family":"Linnenbank","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Section Clinical Anatomy & Embryology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Human Genetics, Leiden University Medical Centre (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-8791","authenticated-orcid":false,"given":"Rene","family":"Van Den Berg","sequence":"additional","affiliation":[{"name":"Department Radiology and Nuclear Medicine, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geerling","family":"Langenbach","sequence":"additional","affiliation":[{"name":"Department of Oral Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081 LA  Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-9061","authenticated-orcid":false,"given":"Karel","family":"de Bree","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-5390","authenticated-orcid":false,"given":"Jaco","family":"Hagoort","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Section Clinical Anatomy & Embryology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4760-3269","authenticated-orcid":false,"given":"Berrie","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Dijklander Hospital, 1624 NP Hoorn, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-8307","authenticated-orcid":false,"given":"Roelof Jan","family":"Oostra","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Section Clinical Anatomy & Embryology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9877-7640","authenticated-orcid":false,"given":"Frank","family":"Lobbezoo","sequence":"additional","affiliation":[{"name":"Department of Oral Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081 LA  Amsterdam, The Netherlands"},{"name":"Department of Orofacial Pain and Jaw Function, Faculty of Odontology, Malm\u00f6 University, 214 21 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5798-5360","authenticated-orcid":false,"given":"Victor","family":"Volovici","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Complex Microvascular Surgery, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-4064","authenticated-orcid":false,"given":"Bernadette Simone","family":"de Bakker","sequence":"additional","affiliation":[{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ  Amsterdam, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC Location AMC, 1105 AZ  Amsterdam, The Netherlands"},{"name":"Department of Pediatric Surgery, Erasmus MC\u2014Sophia Children\u2019s Hospital, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global 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