https://hdl.handle.net/20.500.11811/873 2026-04-18T11:02:24Z https://hdl.handle.net/20.500.11811/13341 <em>TFAP2E</em> is implicated in central nervous system, orofacial and maxillofacial anomalies Kalanithy, Jeshurun C.; Mingardo, Enrico; Stegmann, Jil D.; Dhakar, Ramgopal; Dakal, Tikam Chand; Rosenfeld, Jill A.; Tan, Wen-Hann; Coury, Stephanie A.; Woerner, Audrey C.; Sebastian, Jessica; Levy, Paul A.; Fleming, Leah R.; Waffenschmidt, Lea; Lindenberg, Tobias T.; Yilmaz, Öznur; Channab, Khadija; Babra, Bimaljeet K.; Christ, Andrea; Eiberger, Britta; Hölzel, Selina; Vidic, Clara; Häberlein, Felix; Ishorst, Nina; Rodriguez-Gatica, Juan E.; Pezeshkpoor, Behnaz; Kupczyk, Patrick A.; Vanakker, Olivier M.; Loddo, Sara; Novelli, Antonio; Dentici, Maria L.; Becker, Albert; Thiele, Holger; Posey, Jennifer E.; Lupski, James R.; Hilger, Alina C.; Reutter, Heiko M.; Merz, Waltraut M.; Dworschak, Gabriel C.; Odermatt, Benjamin <strong>Background</strong> Previous studies in mouse, <em>Xenopus</em> and zebrafish embryos show strong <em>tfap2e</em> expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 (<em>TFAP2E</em>) in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.<br /> <strong>Methods</strong> Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies. Exome variant prioritisation prompted <em>TFAP2E</em> gene for functional analysis in zebrafish embryos. Embryonic morphology and development were assessed after antisense morpholino (MO) knockdown (KD), CRISPR/Cas9 knockout and overexpression of <em>tfap2e</em> in fluorescent zebrafish reporter lines using in vivo microscopy. Computational structural protein modelling of the identified human variants was performed.<br /> <strong>Results</strong> In total, exome survey identified novel or ultra- rare heterozygous missense variants in <em>TFAP2E</em> in seven individuals from five independent families with predominantly CNS, orofacial and maxillofacial anomalies. One variant was found de novo and another variant segregated in an affected multiplex family. Protein modelling of the identified variants indicated potential distortion of TFAP2E in the transactivation or dimerisation domain. MO KD and CRISPR/Cas9 knockout of <em>tfap2e</em> in zebrafish revealed hydrocephalus and a significant reduction of brain volume, consistent with a microencephaly phenotype. Furthermore, mRNA overexpression of TFAP2E indicates dosage-sensitive phenotype expression. In addition, zebrafish showed orofacial and maxillofacial anomalies following <em>tfap2e</em> KD, recapitulating the human phenotype.<br /> <strong>Conclusion</strong> Our human genetic data and analysis of Tfap2e manipulation in zebrafish indicate a potential role of <em>TFAP2E</em> in human CNS, orofacial and maxillofacial anomalies. 2024-12-23T00:00:00Z https://hdl.handle.net/20.500.11811/13065 Arterial Blood Supply of the Stifle Joint in Horses Schöpper, Hanna; Egerbacher, Monika The vascularization pattern of the equine stifle joint is insufficiently described in the literature, even though there is a growing need for knowledge of the exact blood supply, as (i) arthroscopy and endoscopic surgery techniques are increasingly performed in horses and (ii) ex vivo models of menisci need nutrient supply that mimic the in vivo situation. The aim of this study was to describe the vessels involved in the stifle joint supply and the exact branching pattern of the popliteal artery. Colored latex was injected into the arteries of nine pelvic limbs of equine cadavers (n = 6) to evaluate the occurrences, variations and approximate diameters of vessels that supplied the stifle joints. Next to a branch of the saphenous and descending genicular arteries, eleven branches of the popliteal artery could be described in horses that feed the vascular network of the stifle joint. With a focus on the blood supply of the menisci, a vascularization map was created to show the main influx to these intra-articular structures in detail. These findings are potentially of great importance to both clinicians in preparation of best-suited incisions for arthroscopy and researchers designing new approaches for meniscal studies and choosing suitable animal models. 2024-04-24T00:00:00Z