NDLI: Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Di Peng Koji Ando Melina Hußmann Marleen Gloger Renae Skoczylas Naoki Mochizuki Christer Betsholtz Shigetomo Fukuhara Stefan Schulte-Merker Nathan D. Lawson Katarzyna Koltowska
Abstract	The migration of lymphatic endothelial cells (LECs) is key for the development of the complex and vast lymphatic vascular network that pervades most tissues in an organism. In zebrafish, arterial intersegmental vessels together with chemokines have been shown to promote lymphatic cell migration from the horizontal myoseptum (HM). We observed that emergence of mural cells around the intersegmental arteries coincides with lymphatic departure from HM which raised the possibility that arterial mural cells promote LEC migration. Our live imaging and cell ablation experiments revealed that LECs migrate slower and fail to establish the lymphatic vascular network in the absence of arterial mural cells. We determined that mural cells are a source for the C-X-C motif chemokine 12 (Cxcl12a and Cxcl12b), vascular endothelial growth factor C (Vegfc) and collagen and calcium-binding EGF domain-containing protein 1 (Ccbe1). We showed that chemokine and growth factor signalling function cooperatively to induce robust LEC migration. Specifically, Vegfc-Vegfr3 signalling, but not chemokines, induces extracellular signal-regulated kinase (ERK) activation in LECs, and has an additional pro-survival role in LECs during the migration. Together, the identification of mural cells as a source for signals that guide LEC migration and survival will be important in the future design for rebuilding lymphatic vessels in disease contexts.
e-ISSN	2050084X
DOI	10.7554/eLife.74094
Journal	eLife
Volume Number	11
Language	English
Publisher	eLife Sciences Publications Ltd
Publisher Date	2022-01-01
Publisher Place	United Kingdom
Access Restriction	Open
Subject Keyword	Medicine Science Biology (general) Cxcl12 Lymphatics Lymphangiogenesis Mural Cells Cell Migration Vegfc
Content Type	Text
Resource Type	Article

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