Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.

Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs). Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we devel...

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Autores principales: Krishnakumar Kizhatil, Margaret Ryan, Jeffrey K Marchant, Stephen Henrich, Simon W M John
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/cc3472acad4944769befa94b4ac6df3c
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spelling oai:doaj.org-article:cc3472acad4944769befa94b4ac6df3c2021-11-25T05:33:02ZSchlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.1544-91731545-788510.1371/journal.pbio.1001912https://doaj.org/article/cc3472acad4944769befa94b4ac6df3c2014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25051267/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs). Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we developed a new whole-mount procedure to visualize its development in the context of surrounding tissues. We then applied genetic lineage tracing, specific-fluorescent reporter genes, immunofluorescence, high-resolution confocal microscopy, and three-dimensional (3D) rendering to study SC. Using these techniques, we show that SECs have a unique phenotype that is a blend of both blood and lymphatic endothelial cell phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to adulthood, we show that SC develops from blood vessels through a newly discovered process that we name "canalogenesis." Functional inhibition of KDR (VEGFR2), a critical receptor in initiating angiogenesis, shows that this receptor is required during canalogenesis. Unlike angiogenesis and similar to stages of vasculogenesis, during canalogenesis tip cells divide and form branched chains prior to vessel formation. Differing from both angiogenesis and vasculogenesis, during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis and lymphatic phenotypes. Thus, SC development resembles a blend of vascular developmental programs. These advances define SC as a unique vessel with a combination of blood vascular and lymphatic phenotypes. They are important for dissecting its functions that are essential for ocular health and normal vision.Krishnakumar KizhatilMargaret RyanJeffrey K MarchantStephen HenrichSimon W M JohnPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 12, Iss 7, p e1001912 (2014)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Krishnakumar Kizhatil
Margaret Ryan
Jeffrey K Marchant
Stephen Henrich
Simon W M John
Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
description Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs). Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we developed a new whole-mount procedure to visualize its development in the context of surrounding tissues. We then applied genetic lineage tracing, specific-fluorescent reporter genes, immunofluorescence, high-resolution confocal microscopy, and three-dimensional (3D) rendering to study SC. Using these techniques, we show that SECs have a unique phenotype that is a blend of both blood and lymphatic endothelial cell phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to adulthood, we show that SC develops from blood vessels through a newly discovered process that we name "canalogenesis." Functional inhibition of KDR (VEGFR2), a critical receptor in initiating angiogenesis, shows that this receptor is required during canalogenesis. Unlike angiogenesis and similar to stages of vasculogenesis, during canalogenesis tip cells divide and form branched chains prior to vessel formation. Differing from both angiogenesis and vasculogenesis, during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis and lymphatic phenotypes. Thus, SC development resembles a blend of vascular developmental programs. These advances define SC as a unique vessel with a combination of blood vascular and lymphatic phenotypes. They are important for dissecting its functions that are essential for ocular health and normal vision.
format article
author Krishnakumar Kizhatil
Margaret Ryan
Jeffrey K Marchant
Stephen Henrich
Simon W M John
author_facet Krishnakumar Kizhatil
Margaret Ryan
Jeffrey K Marchant
Stephen Henrich
Simon W M John
author_sort Krishnakumar Kizhatil
title Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
title_short Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
title_full Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
title_fullStr Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
title_full_unstemmed Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
title_sort schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/cc3472acad4944769befa94b4ac6df3c
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