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Class 3 semaphorins negatively regulate dermal lymphatic network formation.

Uchida Y, James JM, Suto F, Mukouyama YS - Biol Open (2015)

Bottom Line: In contrast, Sema3f;Sema3g double mutants display increased lymphatic branching, while Nrp2 mutants exhibit reduced lymphatic branching.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10/6C103, 10 Center Drive, Bethesda, MD 20892, USA.

No MeSH data available.


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SEMA3F-NRP2 signaling is responsible for inhibition of LEC proliferation in limb skin. (A-D) Whole-mount limb skin staining of E14.5 mutants and WT controls with the proliferation marker phosphohistone H3 (pHH3, green) in addition to PROX1 (red) and LYVE1 (blue). Arrowheads indicate pHH3 positive proliferating LECs. Scale bar: 100 µm. (E) Quantification of pHH3+/PROX1+ LECs at E14.5 limb skin. (F) Quantification in genetic interaction analysis of Prox1+ LEC number per area (mm2) in E15.5 limb skin between Nrp2 and Sema3f mutants. Bars represent mean±s.e.m. and sample numbers (the number of limb skins we analyzed) are shown in the bars. *P<0.05 and **P<0.01; NS, not significant by one-way ANOVA with Tukey-HSD multiple comparison test.
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BIO012302F4: SEMA3F-NRP2 signaling is responsible for inhibition of LEC proliferation in limb skin. (A-D) Whole-mount limb skin staining of E14.5 mutants and WT controls with the proliferation marker phosphohistone H3 (pHH3, green) in addition to PROX1 (red) and LYVE1 (blue). Arrowheads indicate pHH3 positive proliferating LECs. Scale bar: 100 µm. (E) Quantification of pHH3+/PROX1+ LECs at E14.5 limb skin. (F) Quantification in genetic interaction analysis of Prox1+ LEC number per area (mm2) in E15.5 limb skin between Nrp2 and Sema3f mutants. Bars represent mean±s.e.m. and sample numbers (the number of limb skins we analyzed) are shown in the bars. *P<0.05 and **P<0.01; NS, not significant by one-way ANOVA with Tukey-HSD multiple comparison test.

Mentions: We next examined whether the increased LEC number results from an increased LEC proliferation in the mutants. LEC proliferation at E14.5 was significantly increased in Nrp2taugfp/taugfp mutants and Sema3f−/− mutants, compared to Sema3glacZ/lacZ mutants and WT controls (Fig. 4A-E).Fig. 4.


Class 3 semaphorins negatively regulate dermal lymphatic network formation.

Uchida Y, James JM, Suto F, Mukouyama YS - Biol Open (2015)

SEMA3F-NRP2 signaling is responsible for inhibition of LEC proliferation in limb skin. (A-D) Whole-mount limb skin staining of E14.5 mutants and WT controls with the proliferation marker phosphohistone H3 (pHH3, green) in addition to PROX1 (red) and LYVE1 (blue). Arrowheads indicate pHH3 positive proliferating LECs. Scale bar: 100 µm. (E) Quantification of pHH3+/PROX1+ LECs at E14.5 limb skin. (F) Quantification in genetic interaction analysis of Prox1+ LEC number per area (mm2) in E15.5 limb skin between Nrp2 and Sema3f mutants. Bars represent mean±s.e.m. and sample numbers (the number of limb skins we analyzed) are shown in the bars. *P<0.05 and **P<0.01; NS, not significant by one-way ANOVA with Tukey-HSD multiple comparison test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582121&req=5

BIO012302F4: SEMA3F-NRP2 signaling is responsible for inhibition of LEC proliferation in limb skin. (A-D) Whole-mount limb skin staining of E14.5 mutants and WT controls with the proliferation marker phosphohistone H3 (pHH3, green) in addition to PROX1 (red) and LYVE1 (blue). Arrowheads indicate pHH3 positive proliferating LECs. Scale bar: 100 µm. (E) Quantification of pHH3+/PROX1+ LECs at E14.5 limb skin. (F) Quantification in genetic interaction analysis of Prox1+ LEC number per area (mm2) in E15.5 limb skin between Nrp2 and Sema3f mutants. Bars represent mean±s.e.m. and sample numbers (the number of limb skins we analyzed) are shown in the bars. *P<0.05 and **P<0.01; NS, not significant by one-way ANOVA with Tukey-HSD multiple comparison test.
Mentions: We next examined whether the increased LEC number results from an increased LEC proliferation in the mutants. LEC proliferation at E14.5 was significantly increased in Nrp2taugfp/taugfp mutants and Sema3f−/− mutants, compared to Sema3glacZ/lacZ mutants and WT controls (Fig. 4A-E).Fig. 4.

Bottom Line: In contrast, Sema3f;Sema3g double mutants display increased lymphatic branching, while Nrp2 mutants exhibit reduced lymphatic branching.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10/6C103, 10 Center Drive, Bethesda, MD 20892, USA.

No MeSH data available.


Related in: MedlinePlus