{"id":{"repo_id":"helsinki","oai_identifier":"oai:helda.helsinki.fi:10138/586637"},"canonical_url":"https://search.dev.ndltd.org/etd/helsinki/oai:helda.helsinki.fi:10138/586637","repository":{"repo_id":"helsinki","name":"University of Helsinki","base_url":"https://helda.helsinki.fi/server/oai/request"},"display":{"title":"The effect of brain-specific VEGF-C deletion on vascular morphology in the brain and skull","abstract":"Vascular endothelial growth factor C (VEGF-C) promotes mainly lymphangiogenesis, but it can also stimulate angiogenesis by binding to VEGFR3 and VEGFR2 on endothelial cell surface. We studied VEGF-C expression by β-galactosidase staining in VegfcLacZ/+ mice. This revealed Vegfc expression in various parts of the brain. To investigate the role of VEGF-C in the brain, we generated Nestin-Cre; Vegfcfl/fl mice, in which we confirmed deletion of Vegfc. Nestin-Cre is expressed in neuronal and glial cell precursors, in which it mediates Cre-lox recombination of the floxed Vegfc allele. The objective of my study was to see if brain-specific deletion of Vegfc would affect the morphology of meningeal (dural) blood vessels or lymphatic vessels (mLV) in the central nervous system. Immunofluorescent staining was used to visualize the vasculature in dura, spinal column, pituitary gland and brain. The deletion caused no obvious effects on the blood vasculature in the analyzed tissues. However, male mice with Vegfc deletion displayed mLV hypoplasia, which was more severe than in females, and they also had swollen paws. Further immunofluorescence analysis of the ears, genotyping of the toes and qPCR analysis of Vegfc expression in the heart, lung and kidney indicated that Vegfc was deleted also outside of the nervous tissue. By searching published papers, we found that the Nestin-Cre transgenic mice can display sex-biased germline recombination of floxed alleles in multiple tissues if the Nestin-driven recombinase is expressed in gametes or too early during mouse development, which could be the case in our experiments. Thus, at present, we can conclude that the VEGF-C deletion did not affect blood vessels in the CNS, but we cannot yet be sure if VEGF-C deletion in neuronal and glial cells affects the mLVs.","abstract_html":"Vascular endothelial growth factor C (VEGF-C) promotes mainly lymphangiogenesis, but it can also stimulate angiogenesis by binding to VEGFR3 and VEGFR2 on endothelial cell surface. We studied VEGF-C expression by β-galactosidase staining in VegfcLacZ/+ mice. This revealed Vegfc expression in various parts of the brain. To investigate the role of VEGF-C in the brain, we generated Nestin-Cre; Vegfcfl/fl mice, in which we confirmed deletion of Vegfc. Nestin-Cre is expressed in neuronal and glial cell precursors, in which it mediates Cre-lox recombination of the floxed Vegfc allele. The objective of my study was to see if brain-specific deletion of Vegfc would affect the morphology of meningeal (dural) blood vessels or lymphatic vessels (mLV) in the central nervous system. Immunofluorescent staining was used to visualize the vasculature in dura, spinal column, pituitary gland and brain. The deletion caused no obvious effects on the blood vasculature in the analyzed tissues. However, male mice with Vegfc deletion displayed mLV hypoplasia, which was more severe than in females, and they also had swollen paws. Further immunofluorescence analysis of the ears, genotyping of the toes and qPCR analysis of Vegfc expression in the heart, lung and kidney indicated that Vegfc was deleted also outside of the nervous tissue. By searching published papers, we found that the Nestin-Cre transgenic mice can display sex-biased germline recombination of floxed alleles in multiple tissues if the Nestin-driven recombinase is expressed in gametes or too early during mouse development, which could be the case in our experiments. Thus, at present, we can conclude that the VEGF-C deletion did not affect blood vessels in the CNS, but we cannot yet be sure if VEGF-C deletion in neuronal and glial cells affects the mLVs.","abstract_has_math":false,"creators":["Rolin, Tinja Emilia"],"institution":"Helsingin yliopisto","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-10-08","date_published":"2024-10-08","updated_at":"2026-07-27T19:56:30Z","subjects":["VEGF-C","VEGFR3","lymphangiogenesis","blood vessels","Nestin","brain","mouse","meningeal lymphatic vessels"],"languages":["eng"],"rights":["In Copyright 1.0"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10138/586637","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Rolin, Tinja Emilia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-10-08T09:09:07Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-09-03T02:45:10Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-10-08"]},{"key":"dc:publisher","label":"Institution","values":["Helsingin yliopisto","University of Helsinki","Helsingfors universitet"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["VEGF-C","VEGFR3","lymphangiogenesis","blood vessels","Nestin","brain","mouse","meningeal lymphatic vessels"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright 1.0"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10138/586637"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Vascular endothelial growth factor C (VEGF-C) promotes mainly lymphangiogenesis, but it can also stimulate angiogenesis by binding to VEGFR3 and VEGFR2 on endothelial cell surface. We studied VEGF-C expression by β-galactosidase staining in VegfcLacZ/+ mice. This revealed Vegfc expression in various parts of the brain. To investigate the role of VEGF-C in the brain, we generated Nestin-Cre; Vegfcfl/fl mice, in which we confirmed deletion of Vegfc. Nestin-Cre is expressed in neuronal and glial cell precursors, in which it mediates Cre-lox recombination of the floxed Vegfc allele. The objective of my study was to see if brain-specific deletion of Vegfc would affect the morphology of meningeal (dural) blood vessels or lymphatic vessels (mLV) in the central nervous system. Immunofluorescent staining was used to visualize the vasculature in dura, spinal column, pituitary gland and brain. The deletion caused no obvious effects on the blood vasculature in the analyzed tissues. However, male mice with Vegfc deletion displayed mLV hypoplasia, which was more severe than in females, and they also had swollen paws. Further immunofluorescence analysis of the ears, genotyping of the toes and qPCR analysis of Vegfc expression in the heart, lung and kidney indicated that Vegfc was deleted also outside of the nervous tissue. By searching published papers, we found that the Nestin-Cre transgenic mice can display sex-biased germline recombination of floxed alleles in multiple tissues if the Nestin-driven recombinase is expressed in gametes or too early during mouse development, which could be the case in our experiments. Thus, at present, we can conclude that the VEGF-C deletion did not affect blood vessels in the CNS, but we cannot yet be sure if VEGF-C deletion in neuronal and glial cells affects the mLVs.","Vaskulär endotelial tillväxtfaktor C (VEGF-C) främjar i första hand lymfangiogenes, men kan även stimulera angiogenes genom att binda sig till VEGFR3 och VEGFR2 på endotelcellernas yta. För att studera VEGF-C använde vi β-galaktosidasfärgning av VegfcLacZ/+ möss, vilket visade att VEGF-C uttrycks i olika delar av hjärnan. För att undersöka betydelsen av VEGF-C i hjärnan, födde vi upp Nestin-Cre; Vegfcfl/fl möss, vars Vegfc deletion bekräftades. Nestin-Cre uttrycks i neurala och gliaprekursorceller, där den förmedlar Cre-lox rekombination av den floxade Vegfc allelen. Målet med min studie var att undersöka om hjärnspecifik deletion av Vegfc påverkar de meningeala (durala) blodkärlens eller lymfkärlens morfologi i det centrala nervsystemet. Immunofluorescensfärgning användes för att visualisera vaskulaturen i dura, ryggraden, hypofysen och hjärnan. Deletionen orsakade inga tydliga effekter på blodkärlen i de analyserade vävnaderna. Däremot visade hanmöss med deleterad Vegfc en hypoplasi av meningeala lymfkärl, vilket var mer uttalat än hos honor, och hanarna uppvisade även svullna tassar. Dessutom indikerade immunofluorescensanalysen av öron, genotyping av tår och qPCR-analys av Vegfc-expression i hjärtat, lungorna och njuren att Vegfc deleterats även utanför nervvävnaden. Genom att granska publicerade artiklar fann vi att transgena Nestin-Cre möss kan uppvisa könsprefererad rekombination av floxade alleler i flera vävnader under gametogenesen, om Nestin-förmedlad rekombination sker i gameter eller alltför tidigt under musens utveckling, vilket kan vara fallet i våra experiment. Därför kan vi för tillfället dra slutsatsen om att deletionen av VEGF-C inte påverkade blodkärlen i det centrala nervsystemet, men vi kan inte vara säkra på om deletionen av VEGF-C i neuronala och gliaceller påverkar meningeala lymfkärlen."]},{"key":"dc:title","label":"Title","values":["The effect of brain-specific VEGF-C deletion on vascular morphology in the brain and skull"]}]}],"canonical_facts":{"dc:creator":["Rolin, Tinja Emilia"],"dc:date.accessioned":["2024-10-08T09:09:07Z"],"dc:date.available":["2025-09-03T02:45:10Z"],"dc:date.issued":["2024-10-08"],"dc:description.abstract":["Vascular endothelial growth factor C (VEGF-C) promotes mainly lymphangiogenesis, but it can also stimulate angiogenesis by binding to VEGFR3 and VEGFR2 on endothelial cell surface. We studied VEGF-C expression by β-galactosidase staining in VegfcLacZ/+ mice. This revealed Vegfc expression in various parts of the brain. To investigate the role of VEGF-C in the brain, we generated Nestin-Cre; Vegfcfl/fl mice, in which we confirmed deletion of Vegfc. Nestin-Cre is expressed in neuronal and glial cell precursors, in which it mediates Cre-lox recombination of the floxed Vegfc allele. The objective of my study was to see if brain-specific deletion of Vegfc would affect the morphology of meningeal (dural) blood vessels or lymphatic vessels (mLV) in the central nervous system. Immunofluorescent staining was used to visualize the vasculature in dura, spinal column, pituitary gland and brain. The deletion caused no obvious effects on the blood vasculature in the analyzed tissues. However, male mice with Vegfc deletion displayed mLV hypoplasia, which was more severe than in females, and they also had swollen paws. Further immunofluorescence analysis of the ears, genotyping of the toes and qPCR analysis of Vegfc expression in the heart, lung and kidney indicated that Vegfc was deleted also outside of the nervous tissue. By searching published papers, we found that the Nestin-Cre transgenic mice can display sex-biased germline recombination of floxed alleles in multiple tissues if the Nestin-driven recombinase is expressed in gametes or too early during mouse development, which could be the case in our experiments. Thus, at present, we can conclude that the VEGF-C deletion did not affect blood vessels in the CNS, but we cannot yet be sure if VEGF-C deletion in neuronal and glial cells affects the mLVs.","Vaskulär endotelial tillväxtfaktor C (VEGF-C) främjar i första hand lymfangiogenes, men kan även stimulera angiogenes genom att binda sig till VEGFR3 och VEGFR2 på endotelcellernas yta. För att studera VEGF-C använde vi β-galaktosidasfärgning av VegfcLacZ/+ möss, vilket visade att VEGF-C uttrycks i olika delar av hjärnan. För att undersöka betydelsen av VEGF-C i hjärnan, födde vi upp Nestin-Cre; Vegfcfl/fl möss, vars Vegfc deletion bekräftades. Nestin-Cre uttrycks i neurala och gliaprekursorceller, där den förmedlar Cre-lox rekombination av den floxade Vegfc allelen. Målet med min studie var att undersöka om hjärnspecifik deletion av Vegfc påverkar de meningeala (durala) blodkärlens eller lymfkärlens morfologi i det centrala nervsystemet. Immunofluorescensfärgning användes för att visualisera vaskulaturen i dura, ryggraden, hypofysen och hjärnan. Deletionen orsakade inga tydliga effekter på blodkärlen i de analyserade vävnaderna. Däremot visade hanmöss med deleterad Vegfc en hypoplasi av meningeala lymfkärl, vilket var mer uttalat än hos honor, och hanarna uppvisade även svullna tassar. Dessutom indikerade immunofluorescensanalysen av öron, genotyping av tår och qPCR-analys av Vegfc-expression i hjärtat, lungorna och njuren att Vegfc deleterats även utanför nervvävnaden. Genom att granska publicerade artiklar fann vi att transgena Nestin-Cre möss kan uppvisa könsprefererad rekombination av floxade alleler i flera vävnader under gametogenesen, om Nestin-förmedlad rekombination sker i gameter eller alltför tidigt under musens utveckling, vilket kan vara fallet i våra experiment. Därför kan vi för tillfället dra slutsatsen om att deletionen av VEGF-C inte påverkade blodkärlen i det centrala nervsystemet, men vi kan inte vara säkra på om deletionen av VEGF-C i neuronala och gliaceller påverkar meningeala lymfkärlen."],"dc:identifier.uri":["http://hdl.handle.net/10138/586637"],"dc:language.iso":["eng"],"dc:publisher":["Helsingin yliopisto","University of Helsinki","Helsingfors universitet"],"dc:rights":["In Copyright 1.0"],"dc:subject":["VEGF-C","VEGFR3","lymphangiogenesis","blood vessels","Nestin","brain","mouse","meningeal lymphatic vessels"],"dc:title":["The effect of brain-specific VEGF-C deletion on vascular morphology in the brain and skull"]},"updated_at":"2026-07-27T19:56:30Z"}