{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:32:22Z","timestamp":1791873142831,"version":"4.3.4"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Monbl Augenheilkd"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The embryological and fetal morphogenesis of the eyelids and lacrimal drainage\n\t\t\t\t\tsystem is multifactorial and complex. This protracted process begins in the 5th\n\t\t\t\t\tweek of prenatal life and involves a successive series of subtle and tightly\n\t\t\t\t\tregulated morphogenetic events. Major milestones of the embryological and fetal\n\t\t\t\t\tdevelopment of the eyelids include the beginning of eyelid formation during the\n\t\t\t\t\t6th week, eyelid fusion by the 8th week, and the development of eyelid\n\t\t\t\t\tstructures beginning in the 9th week (immediately following eyelid fusion), with\n\t\t\t\t\tprogression until eyelid separation by the 24th week. After eyelid separation,\n\t\t\t\t\tthe eyelids begin to assume their newly developed shape. Around the 32nd week,\n\t\t\t\t\teyelids are almost fully developed and fully separated but still visibly closed.\n\t\t\t\t\tKey development steps of the lacrimal drainage system include formation of the\n\t\t\t\t\tlacrimal lamina (the primordium of the future lacrimal system) and the lacrimal\n\t\t\t\t\tcord (the primordium of the lacrimal canaliculi) in the 7th week, with\n\t\t\t\t\tcanalization starting from the 10th week. During the 10th week, the excretory\n\t\t\t\t\tlacrimal system displays a lumen with a true lacrimal duct that can be\n\t\t\t\t\tdistinguished. The epithelium of the lacrimal canaliculi is in contact with the\n\t\t\t\t\tpalpebral conjunctival epithelium. The two epithelia form a continuous\n\t\t\t\t\tepithelial lamina. The caudal extreme of the lacrimal duct and the inferior\n\t\t\t\t\tmeatal lamina join and the latter begins to cavitate. Understanding this\n\t\t\t\t\tmultidimensional process of development in prenatal life, as well as identifying\n\t\t\t\t\tand linking signaling cascades and regulatory genes to existing diseases, may\n\t\t\t\t\tpave the way for developing minimally invasive interventions and scar reducing\n\t\t\t\t\tsurgical methods, controlling the spread of malignancies, and the use of\n\t\t\t\t\tprogenitor\/stem cell and even regenerative therapy.<\/jats:p>","DOI":"10.1055\/a-1720-9613","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T23:46:24Z","timestamp":1644018384000},"page":"37-45","source":"Crossref","is-referenced-by-count":6,"title":["Embryologic and Fetal Development of the Eyelid and the Lacrimal\n\t\t\t\t\tDrainage System"],"prefix":"10.1055","volume":"239","author":[{"given":"Piotr Jakub","family":"Gaca","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University\n\t\t\t\t\tHospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lewandowicz","sequence":"additional","affiliation":[{"name":"Department of Oncological Surgery, Multidisciplinary M. Copernicus\n\t\t\t\t\tVoivodeship Center for Oncology and Traumatology, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Lipczynska-Lewandowska","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic of Dental and Maxillofacial Surgery, Central\n\t\t\t\t\tClinical Hospital of the Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Simon","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology (CIO) Aachen \u2013 Bonn \u2013 Cologne,\n\t\t\t\t\tDuesseldorf, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philomena A. Wawer","family":"Matos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University\n\t\t\t\t\tHospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Doulis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University\n\t\t\t\t\tHospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C.","family":"Rokohl","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University\n\t\t\t\t\tHospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig M.","family":"Heindl","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University\n\t\t\t\t\tHospital Cologne, University of Cologne, Cologne, Germany"},{"name":"Center for Integrated Oncology (CIO) Aachen \u2013 Bonn \u2013 Cologne,\n\t\t\t\t\tDuesseldorf, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1469-7580.2006.00606.x","article-title":"Morphogenesis of the human excretory lacrimal system","volume":"209","author":"C de la Cuadra-Blanco","year":"2006","journal-title":"J Anat"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1016\/j.ophtha.2009.05.018","article-title":"A surgical strategy for the correction of Fraser syndrome cryptophthalmos","volume":"116","author":"G M Saleh","year":"2009","journal-title":"Ophthalmology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1007\/s00347-016-0426-2","article-title":"[Update on minimally invasive lacrimal drainage surgery]","volume":"114","author":"L M Heindl","year":"2017","journal-title":"Ophthalmologe"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1055\/a-0992-9966","article-title":"[Intubation Systems in Lacrimal Drainage Surgery \u2013 a Current Overview]","volume":"237","author":"A C Rokohl","year":"2020","journal-title":"Klin Monbl Augenheilkd"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/s1534-5807(03)00159-x","article-title":"c-Jun is essential for organization of the epidermal leading edge","volume":"4","author":"G Li","year":"2003","journal-title":"Dev Cell"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/s0092-8674(00)00026-x","article-title":"The EGF receptor provides an essential survival signal for SOS-dependent skin\n\t\t\t\t\ttumor development","volume":"102","author":"M Sibilia","year":"2000","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/s1534-5807(03)00161-8","article-title":"c-Jun regulates eyelid closure and skin tumor development through EGFR\n\t\t\t\t\tsignaling","volume":"4","author":"R Zenz","year":"2003","journal-title":"Dev Cell"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e84858","DOI":"10.1371\/journal.pone.0084858","article-title":"Basal keratinocytes contribute to all strata of the adult zebrafish\n\t\t\t\t\tepidermis","volume":"9","author":"R T Lee","year":"2014","journal-title":"PLoS One"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1097\/IOP.0000000000001172","article-title":"Embryologic and Fetal Development of the Human Orbit","volume":"34","author":"H A Tawfik","year":"2018","journal-title":"Ophthalmic Plast Reconstr Surg"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/j.1469-7580.2007.00773.x","article-title":"The development of the neural crest in the human","volume":"211","author":"R O\u02bcRahilly","year":"2007","journal-title":"J Anat"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/ar.21366","article-title":"Timetable for upper eyelid development in staged human embryos and fetuses","volume":"294","author":"T H Byun","year":"2011","journal-title":"Anat Rec (Hoboken)"},{"key":"ref12","first-page":"1","article-title":"Embryology of the eye and its adnexae","volume":"24","author":"Y R Barishak","year":"1992","journal-title":"Dev Ophthalmol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.ophtha.2016.01.016","article-title":"Conjunctival Mucoepidermoid Carcinoma","volume":"123","author":"K R Koch","year":"2016","journal-title":"Ophthalmology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1755-3768.1967.tb06492.x","article-title":"Histochemistry and development of the human eyelids. 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