Sprouting and anastomosis in the Drosophila trachea and the vertebrate vasculature: similarities and differences in cell behaviour

AbstractBranching morphogenesis is a fascinating process whereby a simple network of biological tubes increases its complexity by adding new branches to existing ones, generating an enlarged structure of interconnected tubes. Branching morphogenesis has been studied extensively in animals and much has been learned about the regulation of branching at the cellular and molecular level. Here, we discuss studies of the Drosophila trachea and of the vertebrate vasculature, which have revealed how new branches are formed and connect (anastomose), leading to the establishment of complex tubular networks. We briefly describe the cell behaviour underlying tracheal and vascular branching. Although similar at many levels, the branching and anastomosis processes characterized thus far show a number of differences in cell behaviour, resulting in somewhat different tube architectures in these two organs. We describe the similarities and the differences and discuss them in the context of their possible developmental significance. We finish by highlighting some old and new data, which suggest that live imaging of the development of capillary beds in adult animals might reveal yet unexplored endothelial behaviour of endothelial cells.

Download Full-text

Sprouting and anastomosis in the Drosophila trachea and the vertebrate vasculature: Similarities and differences in cell behaviour

Vascular Pharmacology ◽

10.1016/j.vph.2018.11.002 ◽

2019 ◽

Vol 112 ◽

pp. 8-16 ◽

Cited By ~ 6

Author(s):

Maria Paraskevi Kotini ◽

Maarja Andaloussi Mäe ◽

Heinz-Georg Belting ◽

Christer Betsholtz ◽

Markus Affolter

Keyword(s):

Cell Behaviour ◽

Similarities And Differences ◽

Drosophila Trachea

Download Full-text

Structure and Function of a Vimentin-associated Matrix Adhesion in Endothelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.12.1.85 ◽

2001 ◽

Vol 12 (1) ◽

pp. 85-100 ◽

Cited By ~ 111

Author(s):

Meredith Gonzales ◽

Babette Weksler ◽

Daisuke Tsuruta ◽

Robert D. Goldman ◽

Kristine J. Yoon ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factors ◽

Endothelial Cell ◽

Branching Morphogenesis ◽

Basement Membranes ◽

Αvβ3 Integrin ◽

Dependent Manner ◽

Matrix Adhesion ◽

Focal Contacts

The α4 laminin subunit is a component of endothelial cell basement membranes. An antibody (2A3) against the α4 laminin G domain stains focal contact-like structures in transformed and primary microvascular endothelial cells (TrHBMECs and HMVECs, respectively), provided the latter cells are activated with growth factors. The 2A3 antibody staining colocalizes with that generated by αv and β3 integrin antibodies and, consistent with this localization, TrHBMECs and HMVECs adhere to the α4 laminin subunit G domain in an αvβ3-integrin–dependent manner. The αvβ3 integrin/2A3 antibody positively stained focal contacts are recognized by vinculin antibodies as well as by antibodies against plectin. Unusually, vimentin intermediate filaments, in addition to microfilament bundles, interact with many of the αvβ3 integrin-positive focal contacts. We have investigated the function of α4-laminin and αvβ3-integrin, which are at the core of these focal contacts, in cultured endothelial cells. Antibodies against these proteins inhibit branching morphogenesis of TrHBMECs and HMVECs in vitro, as well as their ability to repopulate in vitro wounds. Thus, we have characterized an endothelial cell matrix adhesion, which shows complex cytoskeletal interactions and whose assembly is regulated by growth factors. Our data indicate that this adhesion structure may play a role in angiogenesis.

Download Full-text

Abstract 7: LPA/PKD-1-HDAC7-FoxO1 Signaling-mediated Endothelial CD36 Transcriptional Repression and Proarteriogenic Reprogramming

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.7 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Bin Ren ◽

Brad Best ◽

Devi Ramakrishnan ◽

Brian Walcott ◽

Peter Storz ◽

...

Keyword(s):

Endothelial Cells ◽

Transcriptional Repression ◽

Gene Array ◽

Branching Morphogenesis ◽

Gene Profiling ◽

Molecular Signature ◽

Cd36 Deficiency ◽

Angiogenesis Assay ◽

Thrombotic Diseases

Background: CD36 is a scavenger and antiangiogenic receptor that plays an important role in athero-thrombotic diseases, diabetes and cancer and contributes to obesity. Lysophosphatidic acid (LPA), a bioactive phospholipid signaling mediator, abolishes endothelial cell responses to antiangiogenic proteins containing thrombospondin type 1 homology domains by down-regulating endothelial CD36 transcription via protein kinase PKD-1 signaling. However, the precise mechanism as to how angiogenic signaling is integrated to regulate endothelial specific CD36 transcription remain unknown. Hypothesis: LPA represses CD36 transcription through PKD-1-mediated formation of a nuclear transcriptional complex in endothelial cells. Methods: Microvascular endothelial cells expressing CD36 were used for studying signaling and CD36 transcription by real time RT-qPCR, Western blotting, co-immunoprecipitation or avidin-biotin-conjugated DNA-binding assay; angiogenesis gene array was used for angiogenic gene profiling in response to LPA exposure. Spheroid-based angiogenesis assay, in vivo Matrigel assay and tumor angiogenesis model in CD36 deficiency and wild type mice were established to elucidate mechanisms of angiogenic signaling. Results: CD36 transcriptional repression involved PKD-1 signaling mediated formation of FoxO1-HDAC7 complex in the nucleus of endothelial cells. Unexpectedly, turning off CD36 transcription initiated reprogramming MVECs to express ephrin B2, a critical “molecular signature” involved in angiogenesis and arteriogenesis, and increased phosphorylation of Erk1/2, the MAP kinase important in arterial differentiation. PKD-1 signaling was also shown in tumor endothelium of Lewis lung carcinomas, along with low CD36 expression or CD36 deficiency. Angiogenic branching morphogenesis and in vivo angiogenesis were dependent on PKD-1 signaling. Conclusion: LPA/PKD1-HDAC7-FoxO1 signaling axis regulates endothelial CD36 transcription and mediates silencing of the antiangiogenic switch, resulting in proarteriogenic reprogramming. Targeting this signaling cascade could be a novel approach for cancer, diabetes, athero-thrombotic diseases and obesity.

Download Full-text

Whole-mount Immunohistochemical Analysis for Embryonic Limb Skin Vasculature: a Model System to Study Vascular Branching Morphogenesis in Embryo

Journal of Visualized Experiments ◽

10.3791/2620 ◽

2011 ◽

Cited By ~ 2

Author(s):

Wenling Li ◽

Yoh-suke Mukouyama

Keyword(s):

Immunohistochemical Analysis ◽

Branching Morphogenesis ◽

Model System ◽

Whole Mount ◽

Embryonic Limb ◽

Vascular Branching

Download Full-text

Abstract 5566: Recovery of Erk Signaling Restores Defective Angiogenesis and Arteriogenesis in Synectin-Deficient Animals

Circulation ◽

10.1161/circ.118.suppl_18.s_576-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Bin Ren ◽

Arpita Mukhopadhyay* ◽

Anthony A Lanahan ◽

Zhen W Zhuang ◽

Karen L Moodie ◽

...

Keyword(s):

Endothelial Cells ◽

Branching Morphogenesis ◽

Erk Signaling ◽

Dependent Manner ◽

Wild Type ◽

Erk Activation ◽

Arterial Development ◽

Constitutively Active

Background : Arterial morphogenesis is an important and poorly understood process. We have previously demonstrated that disruption of synectin gene expression in mice and zebrafish results in impaired arterial development and branching morphogenesis. Synectin null endothelial cells demonstrate reduced VEGF responsiveness in terms of migration, proliferation and differentiation and ERK-1/2 activation (Chittenden et al, Dev Cell 2006). Since ERK has been established as major participants in the regulation of cell growth and differentiation and Erk activation has been previously linked to arterial morphogenesis, we evaluated whether activation of Erk signaling in synectin disrupted mice and zebrafish as well as synectin KO arterial endothelial cells (ECs) would restore defective migration, arterial differentiation, angiogenesis and arteriogenesis. To stimulate ERK signaling we used partial inhibition of PI3-K activity to reduce Akt-dependent suppression of Raf1 activation or introduction of constitutively active ERK construct. Methods : In vitro studies were conducted with primary arterial ECs isolated from synectin wild type (WT) and knock out (KO) mice. In vivo studies were carried out in WT and synectin deficient mice and synectin knockdown zebrafish embryos. Results: Exposure of synectin −/− arterial EC to two selective PI3K inhibitors GS4898 or LY294002 in vitro restored ERK activation in a dose-dependent manner and returned cell migration and in vitro branching morphogenesis to wild type levels. Transduction of a constitutively active ERK construct in vitro or in a Matrigel model in vivo had similar effect. Systemic treatment of synectin −/− mice with GS4898 fully restored impaired angiogenesis and arterial morphogenesis in adult animals in the setting of hindlimb ischemia. Similar treatment nearly completely restored arterial development defects in zebrafish treated with a synectin morpholino. Conclusions: ERK activation plays a key role in arteriogenesis both in adult tissues and during embryonic development. Activation of compromised ERK-1/2 signaling may be a novel therapeutic intervention to stimulate arteriogenesis.

Download Full-text