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Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

Cattin AL, Burden JJ, Van Emmenis L, Mackenzie FE, Hoving JJ, Garcia Calavia N, Guo Y, McLaughlin M, Rosenberg LH, Quereda V, Jamecna D, Napoli I, Parrinello S, Enver T, Ruhrberg C, Lloyd AC - Cell (2015)

Bottom Line: Here we show that blood vessels direct the migrating cords of Schwann cells.Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair.This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.

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Newly Formed Blood Vessels in the Bridge Are Polarized in the Direction of SC Migration(A) Representative longitudinal sections of a rat sciatic nerve bridge and the contralateral uninjured nerve, day 3 after transection, and 12 hr after EdU injection. EdU+ cells (red) were co-labeled to detect ECs (blue) and S100 to detect SCs (green). Scale bar, 25 μm. White arrowheads indicate EdU+ ECs.(B) Quantification of the proportion of EdU+ ECs in the bridge, day 3 after transection compared to uncut (n = 4).(C) Representative confocal image of a longitudinal section of a rat nerve bridge immunostained for ECs (RECA-1+) at day 3 after transection. Scale bar, 50 μm. Arrow indicates the direction of axonal growth from the proximal (P) to the distal (D) stump.(D) Representative confocal image of a longitudinal section of a mouse nerve bridge immunostained for ECs (CD31+) at Day 5 after transection. Scale bar, 100 μm. For reconstruction of longitudinal sections shown in (C) and (D), multiple images from the same sample were acquired using the same microscope settings.(E and F) Quantification of the proportion of blood vessels parallel or perpendicular to the direction of SC migration in the rat bridge (E) or the mouse bridge (F) (n = 4).Graphs show mean value ± SEM. See also Figure S2.
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fig2: Newly Formed Blood Vessels in the Bridge Are Polarized in the Direction of SC Migration(A) Representative longitudinal sections of a rat sciatic nerve bridge and the contralateral uninjured nerve, day 3 after transection, and 12 hr after EdU injection. EdU+ cells (red) were co-labeled to detect ECs (blue) and S100 to detect SCs (green). Scale bar, 25 μm. White arrowheads indicate EdU+ ECs.(B) Quantification of the proportion of EdU+ ECs in the bridge, day 3 after transection compared to uncut (n = 4).(C) Representative confocal image of a longitudinal section of a rat nerve bridge immunostained for ECs (RECA-1+) at day 3 after transection. Scale bar, 50 μm. Arrow indicates the direction of axonal growth from the proximal (P) to the distal (D) stump.(D) Representative confocal image of a longitudinal section of a mouse nerve bridge immunostained for ECs (CD31+) at Day 5 after transection. Scale bar, 100 μm. For reconstruction of longitudinal sections shown in (C) and (D), multiple images from the same sample were acquired using the same microscope settings.(E and F) Quantification of the proportion of blood vessels parallel or perpendicular to the direction of SC migration in the rat bridge (E) or the mouse bridge (F) (n = 4).Graphs show mean value ± SEM. See also Figure S2.

Mentions: Analysis of the incorporation of EdU found that all the blood vessels within the bridge contained EdU-positive ECs, confirming that they were newly formed (Figures 2A, 2B, and S2A). In contrast, EdU-positive ECs were not found within uncut nerve (Figures 2A and 2B) or in the proximal or distal stumps (Figure S2B). Moreover, erythrocyte staining and the detection of injected immunolabeled-lectin showed that the majority of the newly formed blood vessels within the bridge were functional (Figures S2C and S2D).


Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

Cattin AL, Burden JJ, Van Emmenis L, Mackenzie FE, Hoving JJ, Garcia Calavia N, Guo Y, McLaughlin M, Rosenberg LH, Quereda V, Jamecna D, Napoli I, Parrinello S, Enver T, Ruhrberg C, Lloyd AC - Cell (2015)

Newly Formed Blood Vessels in the Bridge Are Polarized in the Direction of SC Migration(A) Representative longitudinal sections of a rat sciatic nerve bridge and the contralateral uninjured nerve, day 3 after transection, and 12 hr after EdU injection. EdU+ cells (red) were co-labeled to detect ECs (blue) and S100 to detect SCs (green). Scale bar, 25 μm. White arrowheads indicate EdU+ ECs.(B) Quantification of the proportion of EdU+ ECs in the bridge, day 3 after transection compared to uncut (n = 4).(C) Representative confocal image of a longitudinal section of a rat nerve bridge immunostained for ECs (RECA-1+) at day 3 after transection. Scale bar, 50 μm. Arrow indicates the direction of axonal growth from the proximal (P) to the distal (D) stump.(D) Representative confocal image of a longitudinal section of a mouse nerve bridge immunostained for ECs (CD31+) at Day 5 after transection. Scale bar, 100 μm. For reconstruction of longitudinal sections shown in (C) and (D), multiple images from the same sample were acquired using the same microscope settings.(E and F) Quantification of the proportion of blood vessels parallel or perpendicular to the direction of SC migration in the rat bridge (E) or the mouse bridge (F) (n = 4).Graphs show mean value ± SEM. See also Figure S2.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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fig2: Newly Formed Blood Vessels in the Bridge Are Polarized in the Direction of SC Migration(A) Representative longitudinal sections of a rat sciatic nerve bridge and the contralateral uninjured nerve, day 3 after transection, and 12 hr after EdU injection. EdU+ cells (red) were co-labeled to detect ECs (blue) and S100 to detect SCs (green). Scale bar, 25 μm. White arrowheads indicate EdU+ ECs.(B) Quantification of the proportion of EdU+ ECs in the bridge, day 3 after transection compared to uncut (n = 4).(C) Representative confocal image of a longitudinal section of a rat nerve bridge immunostained for ECs (RECA-1+) at day 3 after transection. Scale bar, 50 μm. Arrow indicates the direction of axonal growth from the proximal (P) to the distal (D) stump.(D) Representative confocal image of a longitudinal section of a mouse nerve bridge immunostained for ECs (CD31+) at Day 5 after transection. Scale bar, 100 μm. For reconstruction of longitudinal sections shown in (C) and (D), multiple images from the same sample were acquired using the same microscope settings.(E and F) Quantification of the proportion of blood vessels parallel or perpendicular to the direction of SC migration in the rat bridge (E) or the mouse bridge (F) (n = 4).Graphs show mean value ± SEM. See also Figure S2.
Mentions: Analysis of the incorporation of EdU found that all the blood vessels within the bridge contained EdU-positive ECs, confirming that they were newly formed (Figures 2A, 2B, and S2A). In contrast, EdU-positive ECs were not found within uncut nerve (Figures 2A and 2B) or in the proximal or distal stumps (Figure S2B). Moreover, erythrocyte staining and the detection of injected immunolabeled-lectin showed that the majority of the newly formed blood vessels within the bridge were functional (Figures S2C and S2D).

Bottom Line: Here we show that blood vessels direct the migrating cords of Schwann cells.Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair.This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.

Show MeSH
Related in: MedlinePlus