Cargando…

Class 3 semaphorins negatively regulate dermal lymphatic network formation

The development of a patterned lymphatic vascular network is essential for proper lymphatic functions during organ development and homeostasis. Here we report that class 3 semaphorins (SEMA3s), SEMA3F and SEMA3G negatively regulate lymphatic endothelial cell (LEC) growth and sprouting to control der...

Descripción completa

Detalles Bibliográficos
Autores principales: Uchida, Yutaka, James, Jennifer M., Suto, Fumikazu, Mukouyama, Yoh-suke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582121/
https://www.ncbi.nlm.nih.gov/pubmed/26319580
http://dx.doi.org/10.1242/bio.012302
_version_ 1782391653854609408
author Uchida, Yutaka
James, Jennifer M.
Suto, Fumikazu
Mukouyama, Yoh-suke
author_facet Uchida, Yutaka
James, Jennifer M.
Suto, Fumikazu
Mukouyama, Yoh-suke
author_sort Uchida, Yutaka
collection PubMed
description The development of a patterned lymphatic vascular network is essential for proper lymphatic functions during organ development and homeostasis. Here we report that class 3 semaphorins (SEMA3s), SEMA3F and SEMA3G negatively regulate lymphatic endothelial cell (LEC) growth and sprouting to control dermal lymphatic network formation. Neuropilin2 (NRP2) functions as a receptor for SEMA3F and SEMA3G, as well as vascular endothelial growth factor C (VEGFC). In culture, Both SEMA3F and SEMA3G inhibit VEGFC-mediated sprouting and proliferation of human dermal LECs. In the developing mouse skin, Sema3f is expressed in the epidermis and Sema3g expression is restricted to arteries, whereas their receptor Nrp2 is preferentially expressed by lymphatic vessels. Both Sema3f;Sema3g double mutants and Nrp2 mutants exhibit increased LEC growth in the skin. In contrast, Sema3f;Sema3g double mutants display increased lymphatic branching, while Nrp2 mutants exhibit reduced lymphatic branching. A targeted mutation in PlexinA1 or PlexinA2, signal transducers forming a receptor complex with NRP2 for SEMA3s, exhibits an increase in LEC growth and lymphatic branching as observed in Sema3f;Sema3g double mutants. Our results provide the first evidence that SEMA3F and SEMA3G function as a negative regulator for dermal lymphangiogenesis in vivo. The reciprocal phenotype in lymphatic branching between Sema3f;Sema3g double mutants and Nrp2 mutants suggest a complex NRP2 function that regulates LEC behavior both positively and negatively, through a binding with VEGFC or SEMA3s.
format Online
Article
Text
id pubmed-4582121
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher The Company of Biologists
record_format MEDLINE/PubMed
spelling pubmed-45821212015-10-02 Class 3 semaphorins negatively regulate dermal lymphatic network formation Uchida, Yutaka James, Jennifer M. Suto, Fumikazu Mukouyama, Yoh-suke Biol Open Research Article The development of a patterned lymphatic vascular network is essential for proper lymphatic functions during organ development and homeostasis. Here we report that class 3 semaphorins (SEMA3s), SEMA3F and SEMA3G negatively regulate lymphatic endothelial cell (LEC) growth and sprouting to control dermal lymphatic network formation. Neuropilin2 (NRP2) functions as a receptor for SEMA3F and SEMA3G, as well as vascular endothelial growth factor C (VEGFC). In culture, Both SEMA3F and SEMA3G inhibit VEGFC-mediated sprouting and proliferation of human dermal LECs. In the developing mouse skin, Sema3f is expressed in the epidermis and Sema3g expression is restricted to arteries, whereas their receptor Nrp2 is preferentially expressed by lymphatic vessels. Both Sema3f;Sema3g double mutants and Nrp2 mutants exhibit increased LEC growth in the skin. In contrast, Sema3f;Sema3g double mutants display increased lymphatic branching, while Nrp2 mutants exhibit reduced lymphatic branching. A targeted mutation in PlexinA1 or PlexinA2, signal transducers forming a receptor complex with NRP2 for SEMA3s, exhibits an increase in LEC growth and lymphatic branching as observed in Sema3f;Sema3g double mutants. Our results provide the first evidence that SEMA3F and SEMA3G function as a negative regulator for dermal lymphangiogenesis in vivo. The reciprocal phenotype in lymphatic branching between Sema3f;Sema3g double mutants and Nrp2 mutants suggest a complex NRP2 function that regulates LEC behavior both positively and negatively, through a binding with VEGFC or SEMA3s. The Company of Biologists 2015-08-28 /pmc/articles/PMC4582121/ /pubmed/26319580 http://dx.doi.org/10.1242/bio.012302 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Uchida, Yutaka
James, Jennifer M.
Suto, Fumikazu
Mukouyama, Yoh-suke
Class 3 semaphorins negatively regulate dermal lymphatic network formation
title Class 3 semaphorins negatively regulate dermal lymphatic network formation
title_full Class 3 semaphorins negatively regulate dermal lymphatic network formation
title_fullStr Class 3 semaphorins negatively regulate dermal lymphatic network formation
title_full_unstemmed Class 3 semaphorins negatively regulate dermal lymphatic network formation
title_short Class 3 semaphorins negatively regulate dermal lymphatic network formation
title_sort class 3 semaphorins negatively regulate dermal lymphatic network formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582121/
https://www.ncbi.nlm.nih.gov/pubmed/26319580
http://dx.doi.org/10.1242/bio.012302
work_keys_str_mv AT uchidayutaka class3semaphorinsnegativelyregulatedermallymphaticnetworkformation
AT jamesjenniferm class3semaphorinsnegativelyregulatedermallymphaticnetworkformation
AT sutofumikazu class3semaphorinsnegativelyregulatedermallymphaticnetworkformation
AT mukouyamayohsuke class3semaphorinsnegativelyregulatedermallymphaticnetworkformation