ArticleBiology open2015
Class 3 semaphorins negatively regulate dermal lymphatic network formation.
Article in Biology open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- A neuro-lymphatic communication guides lymphatic development by CXCL12 and CXCR4 signaling.Development (Cambridge, England) · 2024Article
- Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation.Development (Cambridge, England) · 2024Article
- Review
- Lessons of Vascular Specialization From Secondary Lymphoid Organ Lymphatic Endothelial Cells.Circulation research · 2023Review
- MiR-146b-5p/SEMA3G regulates epithelial-mesenchymal transition in clear cell renal cell carcinoma.Cell division · 2023Article
- The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner.The EMBO journal · 2023Article
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Diverse roles for axon guidance pathways in adult tissue architecture and function.Natural sciences (Weinheim, Germany) · 2022Article
- Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.Cold Spring Harbor perspectives in medicine · 2022Article
- Unique functions for Notch4 in murine embryonic lymphangiogenesis.Angiogenesis · 2022Article
- Systemic Sclerosis Serum Significantly Impairs the Multi-Step Lymphangiogenic Process: in Vitro Evidence.International journal of molecular sciences · 2019Article
- Class-3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression.International journal of molecular sciences · 2019Review
- Comparison of Optical Coherence Tomography Angiography to Indocyanine Green Angiography and Slit Lamp Photography for Corneal Vascularization in an Animal Model.Scientific reports · 2018Observational
- Guidance Molecules in Vascular Smooth Muscle.Frontiers in physiology · 2018Review
- Lymphangiogenesis guidance by paracrine and pericellular factors.Genes & development · 2017Review
- Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency.The American journal of pathology · 2016Article
- Dermal lymphatic dilation in a mouse model of alopecia areata.Experimental and molecular pathology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
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 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.