Class 3 semaphorins negatively regulate dermal lymphatic network formation

Biology Open
Yutaka UchidaYoh-suke Mukouyama

Abstract

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 tha...Continue Reading

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Feb 14, 2016·Developmental Biology·Nijiro NohataJ Silvio Gutkind
Mar 10, 2016·Experimental and Molecular Pathology·John P SundbergHarm HogenEsch
Oct 30, 2016·The American Journal of Pathology·Patrick MuckaDiane R Bielenberg
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Sep 28, 2017·Genes & Development·Kari VaahtomeriKari Alitalo

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Methods Mentioned

BETA
dissection
confocal microscopy
FACS

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