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UXT potentiates angiogenesis by attenuating Notch signaling.

Zhou Y, Ge R, Wang R, Liu F, Huang Y, Liu H, Hao Y, Zhou Q, Wang C - Development (2015)

Bottom Line: This prevents RBP-Jκ/CSL from activation and thus inhibits the consequent gene inductions.Furthermore, blockade of Notch signaling rescues the angiogenesis defect caused by UXT knockdown both in vitro and in vivo.Taken together, the data presented in this study characterize UXT as a novel repressor of Notch signaling, shedding new light on the molecular regulation of angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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UXT modulates endothelial cell migration and cell cycle. (A,B) Confocal time-lapse images (from 19 hpf to 30 hpf) of Tg(kdrl:EGFP)s843 embryos injected with 4 ng of control MO (A) or 4 ng of UXT MO (B). The numbering on the images shows the indicated time points. Scale bars: 50 µm. (C) Quantification of endothelial cell number in the segmental artery sprouts. (D) Quantification of the migration speed of ISV tip cells in control embryos and UXT morphants. (E,F) The inhibitory effect of UXT on cell cycle. (E) Flow cytometric analysis for BrdU incorporation and 7-AAD labeling in wild-type and UXT-deficient HUVECs or UXT-deficient HUVECs treated with 1.5 µM DAPT. (F) Quantification of the percentage of cells in different cell cycle stages. All quantitative data are the mean±s.e.m. (at least three independent experiments);*P<0.05, **P<0.01, ***P<0.001 versus the corresponding control.
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DEV112532F4: UXT modulates endothelial cell migration and cell cycle. (A,B) Confocal time-lapse images (from 19 hpf to 30 hpf) of Tg(kdrl:EGFP)s843 embryos injected with 4 ng of control MO (A) or 4 ng of UXT MO (B). The numbering on the images shows the indicated time points. Scale bars: 50 µm. (C) Quantification of endothelial cell number in the segmental artery sprouts. (D) Quantification of the migration speed of ISV tip cells in control embryos and UXT morphants. (E,F) The inhibitory effect of UXT on cell cycle. (E) Flow cytometric analysis for BrdU incorporation and 7-AAD labeling in wild-type and UXT-deficient HUVECs or UXT-deficient HUVECs treated with 1.5 µM DAPT. (F) Quantification of the percentage of cells in different cell cycle stages. All quantitative data are the mean±s.e.m. (at least three independent experiments);*P<0.05, **P<0.01, ***P<0.001 versus the corresponding control.

Mentions: To elucidate the cellular function of UXT, we further investigated ISV formation by in vivo time-lapse confocal microscopy, using Tg(fli1:nEGFP)y7 transgenic fish. Tip cells appeared from the dorsal aorta at around 19 hpf, then they migrated to the horizontal myoseptum (Fig. 4A, 21:31 and 23:43). The majority of tip cells underwent cell divisions two or three times. Ultimately, tip cells migrated dorsally and formed the DLAV normally during ISV formation (Fig. 4A, 26:02 and 29:26). By contrast, tip cells in UXT-deficient Tg(fli1:nEGFP)y7 embryos sprouted late, at ∼23 hpf (Fig. 4B, 20 hpf and 23:28), and then initiated cell divisions at ∼28 hpf (Fig. 4B, 27:34). Remarkably, these tip cells did not migrate further over the horizontal myoseptum (Fig. 4B, 29:38).Fig. 4.


UXT potentiates angiogenesis by attenuating Notch signaling.

Zhou Y, Ge R, Wang R, Liu F, Huang Y, Liu H, Hao Y, Zhou Q, Wang C - Development (2015)

UXT modulates endothelial cell migration and cell cycle. (A,B) Confocal time-lapse images (from 19 hpf to 30 hpf) of Tg(kdrl:EGFP)s843 embryos injected with 4 ng of control MO (A) or 4 ng of UXT MO (B). The numbering on the images shows the indicated time points. Scale bars: 50 µm. (C) Quantification of endothelial cell number in the segmental artery sprouts. (D) Quantification of the migration speed of ISV tip cells in control embryos and UXT morphants. (E,F) The inhibitory effect of UXT on cell cycle. (E) Flow cytometric analysis for BrdU incorporation and 7-AAD labeling in wild-type and UXT-deficient HUVECs or UXT-deficient HUVECs treated with 1.5 µM DAPT. (F) Quantification of the percentage of cells in different cell cycle stages. All quantitative data are the mean±s.e.m. (at least three independent experiments);*P<0.05, **P<0.01, ***P<0.001 versus the corresponding control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325377&req=5

DEV112532F4: UXT modulates endothelial cell migration and cell cycle. (A,B) Confocal time-lapse images (from 19 hpf to 30 hpf) of Tg(kdrl:EGFP)s843 embryos injected with 4 ng of control MO (A) or 4 ng of UXT MO (B). The numbering on the images shows the indicated time points. Scale bars: 50 µm. (C) Quantification of endothelial cell number in the segmental artery sprouts. (D) Quantification of the migration speed of ISV tip cells in control embryos and UXT morphants. (E,F) The inhibitory effect of UXT on cell cycle. (E) Flow cytometric analysis for BrdU incorporation and 7-AAD labeling in wild-type and UXT-deficient HUVECs or UXT-deficient HUVECs treated with 1.5 µM DAPT. (F) Quantification of the percentage of cells in different cell cycle stages. All quantitative data are the mean±s.e.m. (at least three independent experiments);*P<0.05, **P<0.01, ***P<0.001 versus the corresponding control.
Mentions: To elucidate the cellular function of UXT, we further investigated ISV formation by in vivo time-lapse confocal microscopy, using Tg(fli1:nEGFP)y7 transgenic fish. Tip cells appeared from the dorsal aorta at around 19 hpf, then they migrated to the horizontal myoseptum (Fig. 4A, 21:31 and 23:43). The majority of tip cells underwent cell divisions two or three times. Ultimately, tip cells migrated dorsally and formed the DLAV normally during ISV formation (Fig. 4A, 26:02 and 29:26). By contrast, tip cells in UXT-deficient Tg(fli1:nEGFP)y7 embryos sprouted late, at ∼23 hpf (Fig. 4B, 20 hpf and 23:28), and then initiated cell divisions at ∼28 hpf (Fig. 4B, 27:34). Remarkably, these tip cells did not migrate further over the horizontal myoseptum (Fig. 4B, 29:38).Fig. 4.

Bottom Line: This prevents RBP-Jκ/CSL from activation and thus inhibits the consequent gene inductions.Furthermore, blockade of Notch signaling rescues the angiogenesis defect caused by UXT knockdown both in vitro and in vivo.Taken together, the data presented in this study characterize UXT as a novel repressor of Notch signaling, shedding new light on the molecular regulation of angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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