@article{ff884728e27d4f22833f3ff79eaeb1e8,
title = "Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis",
abstract = "Postnatal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage-tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato-positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture-induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT + LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT + lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis.",
author = "Connor, {Alicia L.} and Kelley, {Philip M.} and Tempero, {Richard M.}",
note = "Funding Information: This work was funded by grants from the NIH: National Eye Institute RO1- EY021571 and National Institute of General Medical Sciences, 5 P20 RR018788- 08. Part of this research was conducted at the Integrative Biological Imaging Facility at Creighton University, Omaha, NE, USA (Leica TCS SP8 MP). This facility, supported by the Creighton University School of Medicine, was constructed with support from grants from the National Center for Research Resources (5P20RR016469) and the National Institute for General Medical Science (NIGMS) (8P20GM103427), a component of the NIH. Microscope Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy and the Nebraska Research Initiative and the Eppley Cancer Center for their support of the Core Facility (Zeiss LSM 710). This investigation is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the NIH. We acknowledge Maggie Van Keuren for preparation of transgenic mice and the Transgenic Animal Model Core of the University of Michigan{\textquoteright}s Biomedical Research Core Facilities. Funding Information: This work was funded by grants from the NIH: National Eye Institute RO1-EY021571 and National Institute of General Medical Sciences, 5 P20 RR018788-08. Part of this research was conducted at the Integrative Biological Imaging Facility at Creighton University, Omaha, NE, USA (Leica TCS SP8 MP). This facility, supported by the Creighton University School of Medicine, was constructed with support from grants from the National Center for Research Resources (5P20RR016469) and the National Institute for General Medical Science (NIGMS) (8P20GM103427), a component of the NIH. Microscope Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy and the Nebraska Research Initiative and the Eppley Cancer Center for their support of the Core Facility (Zeiss LSM 710). This investigation is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the NIH. We acknowledge Maggie Van Keuren for preparation of transgenic mice and the Transgenic Animal Model Core of the University of Michigan{\textquoteright}s Biomedical Research Core Facilities. Publisher Copyright: {\textcopyright} 2016 USCAP, Inc.",
year = "2016",
month = mar,
day = "1",
doi = "10.1038/labinvest.2015.147",
language = "English (US)",
volume = "96",
pages = "270--282",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "3",
}