Dynamic Endothelial Cell Rearrangements Drive Developmental Vessel Regression

Franco, Cláudio A.; Jones, Martin L.; Bernabéu, Miguel O.; Geudens, Ilse; Mathivet, Thomas; Rosa, André; Lopes, Felicia M.; Lima, Aida P.; Ragab, Anan; Collins, Russell T.; Phng, Li-Kun; Coveney, Peter V.; Gerhardt, Holger

doi:10.1371/journal.pbio.1002125

Cited by 266 publications

(447 citation statements)

References 34 publications

(48 reference statements)

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“…We did not find evidence at any stage of plexus resolution that would suggest that remodeling is accomplished through breakage and regression of epithelial segments, as reported for vascular plexus remodeling (Franco et al 2015). Rather, we observed an apparent progressive consolidation of epithelial plexus segments that effectively reduces the complexity of, and eventually eliminates, the plexus web to generate the final ductal tree.…”

Section: Distinct Processes Of Plexus-to-duct Remodeling and Epithelisupporting

confidence: 49%

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

2015

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In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the "trunk epithelium." Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial "plexus state," which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium.

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Section: Distinct Processes Of Plexus-to-duct Remodeling and Epithelisupporting

confidence: 49%

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

2015

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“…36,37 Recent detailed analysis of the angiogenic retinal vasculature in mice found that only~5% of regressing vessels found during normal angiogenesis actually contained apoptotic ECs. 38 Whether EC apoptosis is functionally necessary for vessel pruning in the mouse retina is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1

Whitehead

Adams

et al. 2016

Cell Death Differ

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Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dosedependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite the known link between apoptosis and blood vessel regression, this was not the cause of reduced vessel density observed in the absence of endothelial MCL1. Rather, the reduction in vessel density was linked to ectopic apoptosis in regions of the angiogenic vasculature where EC proliferation and new vessel growth occurs. We have therefore identified MCL1 as an essential survival factor for ECs that is required for blood vessel production during angiogenesis.

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“…A further distinction between types of vasoregression has been proposed, dependent on the persistence of a patent lumen of the regressive capillary branch (type 1 pruning, closed lumen, resulting from low shear stress/non-perfusion; type 2 pruning, open lumen, high shear stress/perfusion). In this context, blood flow is a critical determinant, since vasoconstriction induces vasoregression while enhanced blood flow protects against vasoregression [28,29].…”

Section: The Importance Of Vasoregressionmentioning

confidence: 99%

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

2017

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Diabetic retinopathy remains a relevant clinical problem. In parallel with diagnostic and therapeutic improvements, the role of glycaemia and reactive metabolites causing cell stress and biochemical abnormalities as treatment targets needs continuous re-evaluation. Furthermore, the basic mechanisms of physiological angiogenesis, remodelling and pruning give important clues about the origins of vasoregression during the very early stages of diabetic retinopathy and can be modelled in animals. This review summarises evidence supporting a role for the neurovascular unit-composed of neuronal, glial and vascular cells-as a responder to the biochemical changes imposed by reactive metabolites and high glucose. Normoglycaemic animal models developing retinal degeneration, provide valuable information about common pathways downstream of progressive neuronal damage that induce vasoregression, as in diabetic models. These models can serve to assess novel treatments addressing the entire neurovascular unit for the benefit of early diabetic retinopathy. Diabetic retinopathy: the danger is not overThe overall prevalence of diabetic retinopathy is 35% among people with diabetes worldwide, with a current decline in both any retinopathy and sight-threatening stages [1]. Diabetic retinopathy ranks fifth among common causes for blindness or severe vision impairment and a recent meta-analysis revealed that the age-standardised prevalence of diabetic retinopathyrelated blindness will increase due to increasing populations and average age together with a reduction in death rates [2]. Lending support to the magnitude of the problem are reports that even when a person first presents at screening services, advanced diabetic retinopathy is present at levels that are no longer amenable to medical interventions [3,4]. Recent population-based studies from Europe revealed that screening-detected diabetic retinopathy appeared in more thanElectronic supplementary material The online version of this article (https://doi

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Dynamic Endothelial Cell Rearrangements Drive Developmental Vessel Regression

Cited by 266 publications

References 34 publications

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

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