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Endothelial cell self-fusion during vascular pruning.

Lenard A, Daetwyler S, Betz C, Ellertsdottir E, Belting HG, Huisken J, Affolter M - PLoS Biol. (2015)

Bottom Line: Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail.In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection.Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum der Universität Basel, Basel, Switzerland.

ABSTRACT
During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.

No MeSH data available.


Related in: MedlinePlus

Two cellular models of vascular pruning.A pruning branch is initially a multicellular tube (A). The cellular rearrangements to follow depend on collapse or maintenance of lumen at this stage (pruning type I or II, respectively). If the lumen collapses before cell rearrangements (type I pruning, B’), cell rearrangements lead to formation of a unicellular connection (C’–D’). The last linking cell regresses (E’) and completely resolves the last connection (F’) to complete the pruning process (G). If the lumen is maintained, cell rearrangements lead most cells out of the branch (B‘‘, arrows) and force the remaining cell to undergo self-fusion and form a unicellular tube (C”, arrow). Transcellular lumen collapses in the unicellular tube, forming two separate luminal compartments (D”, arrows). The last cell reduces its contact to one of the major branches (E”) and eventually the last contact (F”) is resolved and pruning is complete (G). See also S6 Fig.
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pbio.1002126.g006: Two cellular models of vascular pruning.A pruning branch is initially a multicellular tube (A). The cellular rearrangements to follow depend on collapse or maintenance of lumen at this stage (pruning type I or II, respectively). If the lumen collapses before cell rearrangements (type I pruning, B’), cell rearrangements lead to formation of a unicellular connection (C’–D’). The last linking cell regresses (E’) and completely resolves the last connection (F’) to complete the pruning process (G). If the lumen is maintained, cell rearrangements lead most cells out of the branch (B‘‘, arrows) and force the remaining cell to undergo self-fusion and form a unicellular tube (C”, arrow). Transcellular lumen collapses in the unicellular tube, forming two separate luminal compartments (D”, arrows). The last cell reduces its contact to one of the major branches (E”) and eventually the last contact (F”) is resolved and pruning is complete (G). See also S6 Fig.

Mentions: Upon initiation of blood vessel regression, endothelial cells migrate out of the regressing branch. This behavior is regulated by a change in cell polarity, which itself appears to be controlled by hemodynamic forces (see accompanying article [27]). Our analyses are in agreement with this view and show that these cell rearrangements and especially the lumen collapse are highly dynamic processes that are strongly influenced by the presence of blood pressure in the developing vessels. During SIV pruning, endothelial cells can embark on two different morphogenetic pathways, of which only type II pruning involves cell wrapping and cell self-fusion (Fig 6). At this point, we do not have evidence whether a particular signaling pathway regulates the choice of the morphogenetic pathway. Type I and type II pruning mechanisms split up only after endothelial cells have initiated cell rearrangements, suggesting that neither Notch/Dll nor noncanonical Wnt signaling is directly involved in the determination of type I versus type II specification. In contrast, type I/II pruning strongly correlates with the presence (type II) or absence (type I) of lumen during this process. This correlation suggests that pruning type selection is rather controlled by mechanical cues and that endothelial cells adapt their behavior to different luminal topologies during cell rearrangement.


Endothelial cell self-fusion during vascular pruning.

Lenard A, Daetwyler S, Betz C, Ellertsdottir E, Belting HG, Huisken J, Affolter M - PLoS Biol. (2015)

Two cellular models of vascular pruning.A pruning branch is initially a multicellular tube (A). The cellular rearrangements to follow depend on collapse or maintenance of lumen at this stage (pruning type I or II, respectively). If the lumen collapses before cell rearrangements (type I pruning, B’), cell rearrangements lead to formation of a unicellular connection (C’–D’). The last linking cell regresses (E’) and completely resolves the last connection (F’) to complete the pruning process (G). If the lumen is maintained, cell rearrangements lead most cells out of the branch (B‘‘, arrows) and force the remaining cell to undergo self-fusion and form a unicellular tube (C”, arrow). Transcellular lumen collapses in the unicellular tube, forming two separate luminal compartments (D”, arrows). The last cell reduces its contact to one of the major branches (E”) and eventually the last contact (F”) is resolved and pruning is complete (G). See also S6 Fig.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4401649&req=5

pbio.1002126.g006: Two cellular models of vascular pruning.A pruning branch is initially a multicellular tube (A). The cellular rearrangements to follow depend on collapse or maintenance of lumen at this stage (pruning type I or II, respectively). If the lumen collapses before cell rearrangements (type I pruning, B’), cell rearrangements lead to formation of a unicellular connection (C’–D’). The last linking cell regresses (E’) and completely resolves the last connection (F’) to complete the pruning process (G). If the lumen is maintained, cell rearrangements lead most cells out of the branch (B‘‘, arrows) and force the remaining cell to undergo self-fusion and form a unicellular tube (C”, arrow). Transcellular lumen collapses in the unicellular tube, forming two separate luminal compartments (D”, arrows). The last cell reduces its contact to one of the major branches (E”) and eventually the last contact (F”) is resolved and pruning is complete (G). See also S6 Fig.
Mentions: Upon initiation of blood vessel regression, endothelial cells migrate out of the regressing branch. This behavior is regulated by a change in cell polarity, which itself appears to be controlled by hemodynamic forces (see accompanying article [27]). Our analyses are in agreement with this view and show that these cell rearrangements and especially the lumen collapse are highly dynamic processes that are strongly influenced by the presence of blood pressure in the developing vessels. During SIV pruning, endothelial cells can embark on two different morphogenetic pathways, of which only type II pruning involves cell wrapping and cell self-fusion (Fig 6). At this point, we do not have evidence whether a particular signaling pathway regulates the choice of the morphogenetic pathway. Type I and type II pruning mechanisms split up only after endothelial cells have initiated cell rearrangements, suggesting that neither Notch/Dll nor noncanonical Wnt signaling is directly involved in the determination of type I versus type II specification. In contrast, type I/II pruning strongly correlates with the presence (type II) or absence (type I) of lumen during this process. This correlation suggests that pruning type selection is rather controlled by mechanical cues and that endothelial cells adapt their behavior to different luminal topologies during cell rearrangement.

Bottom Line: Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail.In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection.Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum der Universität Basel, Basel, Switzerland.

ABSTRACT
During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.

No MeSH data available.


Related in: MedlinePlus