Limits...
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.

Show MeSH

Related in: MedlinePlus

Blood Vessels in the Bridge Have Thin Basal Lamina, Allowing Direct Points of Contact with Schwann Cells, Related to Figure 3(A) Representative confocal images of the bridges of rat sciatic nerves, Day 4 after transection, immunostained to detect the indicated matrix proteins (red) and endothelial cells (green). Scale bar = 25 μm.(B) Representative TEM images of blood vessels from the bridge region and the contralateral nerve, Day 5 after transection. Note the basal lamina is thinner, less dense and/or absent around blood vessels within the bridge. Scale bar = 250nm.(C) Quantification of the average thickness of the basal lamina of the blood vessels as described in (B), each point represents a separate blood vessel from 3 independent animals. The red lines represent the mean.(D) Correlative light and electron microscopy of a 100μm thick vibrating microtome cross section of GFP-expressing Schwann cells (green) from a lectin (red) injected mouse sciatic nerve, Day 5 after transection. Panels on the left show a confocal image of GFP–expressing Schwann cells, either alone (top), overlayed on the correlated TEM image (middle) and TEM image alone (bottom). Outlined box highlights the GFP-expressing Schwann cell (SC) interacting with endothelial cells (EC), enlarged in the panels on the left, reconstructed in Figure 3G, and Movie S2. Note the points of direct contact between the Schwann cell and the blood vessel and sporadic/absent basal lamina of both cell types. Scale bars = 20 μm (white), 1 μm (black).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4553238&req=5

figs3: Blood Vessels in the Bridge Have Thin Basal Lamina, Allowing Direct Points of Contact with Schwann Cells, Related to Figure 3(A) Representative confocal images of the bridges of rat sciatic nerves, Day 4 after transection, immunostained to detect the indicated matrix proteins (red) and endothelial cells (green). Scale bar = 25 μm.(B) Representative TEM images of blood vessels from the bridge region and the contralateral nerve, Day 5 after transection. Note the basal lamina is thinner, less dense and/or absent around blood vessels within the bridge. Scale bar = 250nm.(C) Quantification of the average thickness of the basal lamina of the blood vessels as described in (B), each point represents a separate blood vessel from 3 independent animals. The red lines represent the mean.(D) Correlative light and electron microscopy of a 100μm thick vibrating microtome cross section of GFP-expressing Schwann cells (green) from a lectin (red) injected mouse sciatic nerve, Day 5 after transection. Panels on the left show a confocal image of GFP–expressing Schwann cells, either alone (top), overlayed on the correlated TEM image (middle) and TEM image alone (bottom). Outlined box highlights the GFP-expressing Schwann cell (SC) interacting with endothelial cells (EC), enlarged in the panels on the left, reconstructed in Figure 3G, and Movie S2. Note the points of direct contact between the Schwann cell and the blood vessel and sporadic/absent basal lamina of both cell types. Scale bars = 20 μm (white), 1 μm (black).

Mentions: Confocal microscopy analysis of the SCs entering into the bridge demonstrated a close association of the migrating SC cords and the polarized blood vessels (Figure 3A). Moreover, at later time points when the SCs had migrated further into the bridge, these interactions were maintained (Figure 3B). Analysis of matrix components of the bridge showed that fibronectin filled the space between the cells throughout the bridge and that strands of elastin also permeated the bridge region. In contrast, laminin and collagen I and IV could be detected only around the blood vessels (Figure S3A). To quantify the degree and specificity of the interactions between the SCs and the blood vessels, we measured the shortest distance between the nuclei of SCs at the leading edge and their closest blood vessel and compared it to the distance of other cell types present in the bridge. We found that the majority of SCs were extremely close (<10 μm) to blood vessels with the population showing a strong distribution toward the blood vessels, whereas the other cell types had a more random distribution within the bridge (Figure 3C). Moreover, the degree of interaction between SCs and blood vessels was probably underestimated, as we frequently observed SCs interacting with blood vessels via long protrusions while the nuclei were further away.


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)

Blood Vessels in the Bridge Have Thin Basal Lamina, Allowing Direct Points of Contact with Schwann Cells, Related to Figure 3(A) Representative confocal images of the bridges of rat sciatic nerves, Day 4 after transection, immunostained to detect the indicated matrix proteins (red) and endothelial cells (green). Scale bar = 25 μm.(B) Representative TEM images of blood vessels from the bridge region and the contralateral nerve, Day 5 after transection. Note the basal lamina is thinner, less dense and/or absent around blood vessels within the bridge. Scale bar = 250nm.(C) Quantification of the average thickness of the basal lamina of the blood vessels as described in (B), each point represents a separate blood vessel from 3 independent animals. The red lines represent the mean.(D) Correlative light and electron microscopy of a 100μm thick vibrating microtome cross section of GFP-expressing Schwann cells (green) from a lectin (red) injected mouse sciatic nerve, Day 5 after transection. Panels on the left show a confocal image of GFP–expressing Schwann cells, either alone (top), overlayed on the correlated TEM image (middle) and TEM image alone (bottom). Outlined box highlights the GFP-expressing Schwann cell (SC) interacting with endothelial cells (EC), enlarged in the panels on the left, reconstructed in Figure 3G, and Movie S2. Note the points of direct contact between the Schwann cell and the blood vessel and sporadic/absent basal lamina of both cell types. Scale bars = 20 μm (white), 1 μm (black).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553238&req=5

figs3: Blood Vessels in the Bridge Have Thin Basal Lamina, Allowing Direct Points of Contact with Schwann Cells, Related to Figure 3(A) Representative confocal images of the bridges of rat sciatic nerves, Day 4 after transection, immunostained to detect the indicated matrix proteins (red) and endothelial cells (green). Scale bar = 25 μm.(B) Representative TEM images of blood vessels from the bridge region and the contralateral nerve, Day 5 after transection. Note the basal lamina is thinner, less dense and/or absent around blood vessels within the bridge. Scale bar = 250nm.(C) Quantification of the average thickness of the basal lamina of the blood vessels as described in (B), each point represents a separate blood vessel from 3 independent animals. The red lines represent the mean.(D) Correlative light and electron microscopy of a 100μm thick vibrating microtome cross section of GFP-expressing Schwann cells (green) from a lectin (red) injected mouse sciatic nerve, Day 5 after transection. Panels on the left show a confocal image of GFP–expressing Schwann cells, either alone (top), overlayed on the correlated TEM image (middle) and TEM image alone (bottom). Outlined box highlights the GFP-expressing Schwann cell (SC) interacting with endothelial cells (EC), enlarged in the panels on the left, reconstructed in Figure 3G, and Movie S2. Note the points of direct contact between the Schwann cell and the blood vessel and sporadic/absent basal lamina of both cell types. Scale bars = 20 μm (white), 1 μm (black).
Mentions: Confocal microscopy analysis of the SCs entering into the bridge demonstrated a close association of the migrating SC cords and the polarized blood vessels (Figure 3A). Moreover, at later time points when the SCs had migrated further into the bridge, these interactions were maintained (Figure 3B). Analysis of matrix components of the bridge showed that fibronectin filled the space between the cells throughout the bridge and that strands of elastin also permeated the bridge region. In contrast, laminin and collagen I and IV could be detected only around the blood vessels (Figure S3A). To quantify the degree and specificity of the interactions between the SCs and the blood vessels, we measured the shortest distance between the nuclei of SCs at the leading edge and their closest blood vessel and compared it to the distance of other cell types present in the bridge. We found that the majority of SCs were extremely close (<10 μm) to blood vessels with the population showing a strong distribution toward the blood vessels, whereas the other cell types had a more random distribution within the bridge (Figure 3C). Moreover, the degree of interaction between SCs and blood vessels was probably underestimated, as we frequently observed SCs interacting with blood vessels via long protrusions while the nuclei were further away.

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