Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1717-1730 ◽  
Author(s):  
M.A. Dyer ◽  
S.M. Farrington ◽  
D. Mohn ◽  
J.R. Munday ◽  
M.H. Baron
Keyword(s):  
Endothelial Cells ◽  
Cell Fate ◽  
Mouse Embryo ◽  
Hedgehog Signaling ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Indian Hedgehog ◽  
Vascular Endothelial ◽  
Primitive Endoderm ◽  
Genes Encoding

During gastrulation in the mouse, mesoderm is induced and patterned by secreted signaling molecules, giving rise first to primitive erythroblasts and vascular endothelial cells. We have demonstrated previously that development of these lineages requires a signal(s) secreted from the adjacent primitive endoderm. We now show that Indian hedgehog (Ihh) is a primitive endoderm-secreted signal that alone is sufficient to induce formation of hematopoietic and endothelial cells. Strikingly, as seen with primitive endoderm, Ihh can respecify prospective neural ectoderm (anterior epiblast) along hematopoietic and endothelial (posterior) lineages. Downstream targets of the hedgehog signaling pathway (the genes encoding patched, smoothened and Gli1) are upregulated in anterior epiblasts cultured in the presence of Ihh protein, as is Bmp4, which may mediate the effects of Ihh. Blocking Ihh function in primitive endoderm inhibits activation of hematopoiesis and vasculogenesis in the adjacent epiblast, suggesting that Ihh is an endogenous signal that plays a key role in the development of the earliest hemato-vascular system. To our knowledge, these are the earliest functions for a hedgehog protein in post-implantation development in the mouse embryo.

Prox1 expression is negatively regulated by miR-181 in endothelial cells

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2395-2401 ◽  
Author(s):  
Jan Kazenwadel ◽  
Michael Z. Michael ◽  
Natasha L. Harvey
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Lymphatic Endothelial Cell ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Lymphatic Endothelial Cells ◽  
Prox1 Expression

Abstract The specification of arterial, venous, and lymphatic endothelial cell fate is critical during vascular development. Although the homeobox transcription factor, Prox1, is crucial for the specification and maintenance of lymphatic endothelial cell identity, little is known regarding the mechanisms that regulate Prox1 expression. Here we demonstrate that miR-181a binds the 3′ untranslated region of Prox1, resulting in translational inhibition and transcript degradation. Increased miR-181a activity in primary embryonic lymphatic endothelial cells resulted in substantially reduced levels of Prox1 mRNA and protein and reprogramming of lymphatic endothelial cells toward a blood vascular phenotype. Conversely, treatment of primary embryonic blood vascular endothelial cells with miR-181a antagomir resulted in increased Prox1 mRNA levels. miR-181a expression is significantly higher in embryonic blood vascular endothelial cells compared with lymphatic endothelial cells, suggesting that miR-181 activity could be an important mechanism by which Prox1 expression is silenced in the blood vasculature during development. Our work is the first example of a microRNA that targets Prox1 and has implications for the control of Prox1 expression during vascular development and neo-lymphangiogenesis.

scholarly journals Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective

2021 ◽  
Vol 9 ◽  
Author(s):  
Abdellah Akil ◽  
Ana K. Gutiérrez-García ◽  
Rachael Guenter ◽  
J. Bart Rose ◽  
Adam W. Beck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Progression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Notch Pathway ◽  
Vascular Endothelial ◽  
Cell Fate Determination ◽  
Fate Determination

The Notch signaling pathway plays an essential role in a wide variety of biological processes including cell fate determination of vascular endothelial cells and the regulation of arterial differentiation and angiogenesis. The Notch pathway is also an essential regulator of tumor growth and survival by functioning as either an oncogene or a tumor suppressor in a context-dependent manner. Crosstalk between the Notch and other signaling pathways is also pivotal in tumor progression by promoting cancer cell growth, migration, invasion, metastasis, tumor angiogenesis, and the expansion of cancer stem cells (CSCs). In this review, we provide an overview and update of Notch signaling in endothelial cell fate determination and functioning, angiogenesis, and tumor progression, particularly in the development of CSCs and therapeutic resistance. We further summarize recent studies on how endothelial signaling crosstalk with the Notch pathway contributes to tumor angiogenesis and the development of CSCs, thereby providing insights into vascular biology within the tumor microenvironment and tumor progression.

scholarly journals The expression and localization of RNase and RNase inhibitor in blood cells and vascular endothelial cells in homeostasis of the vascular system

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0174237 ◽  
Author(s):  
Ayaka Ohashi ◽  
Aya Murata ◽  
Yuichiro Cho ◽  
Shizuko Ichinose ◽  
Yuriko Sakamaki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Cells ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Rnase Inhibitor

scholarly journals Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Susov Dhakal ◽  
Shahar Rotem-Bamberger ◽  
Josilyn R. Sejd ◽  
Meyrav Sebbagh ◽  
Nathan Ronin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Endothelial Cell ◽  
Cell Differentiation ◽  
Gas Exchange ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Retinal Development ◽  
Vascular Endothelial ◽  
Vertebrate Eye

Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. The retinal phenotypes in these genetic systems were not identical, with endothelial cell-depleted retinas displaying laminar disorganization, cell death, reduced proliferation, and reduced cell differentiation. In contrast, the lack of blood flow resulted in a milder retinal phenotype showing reduced proliferation and reduced cell differentiation, indicating that an endothelial cell-derived factor(s) is/are required for laminar organization and cell survival. The lack of erythrocytes did not result in an obvious retinal phenotype, confirming that defects in retinal development that result from vascular manipulations are not due to poor gas exchange. These findings underscore the importance of the cardiovascular system supporting and controlling retinal development in ways other than supplying oxygen. In addition, these findings identify a key developmental window for these interactions and point to distinct functions for vascular endothelial cells vs. circulating factors.

scholarly journals Vascular Notch Signaling in Stress Hematopoiesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Can Huang ◽  
Dawei Yang ◽  
George W. Ye ◽  
Charles A. Powell ◽  
Peipei Guo
Keyword(s):  
Endothelial Cells ◽  
Notch Signaling ◽  
Cell Fate ◽  
Stromal Cell ◽  
Vascular Endothelial Cells ◽  
Cell Lineage ◽  
Transgenic Animals ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Hematopoietic Stem

Canonical Notch signaling is one of the most conserved signaling cascades. It regulates cell proliferation, cell differentiation, and cell fate maintenance in a variety of biological systems during development and cancer (Fortini, 2009; Kopan and Ilagan, 2009; Andersson et al., 2011; Ntziachristos et al., 2014). For the hematopoietic system, during embryonic development, Notch1 is essential for the emergence of hematopoietic stem cells (HSCs) at the aorta-gornado-mesonephro regions of the dorsal aorta. At adult stage, Notch receptors and Notch targets are expressed at different levels in diverse hematopoietic cell types and influence lineage choices. For example, Notch specifies T cell lineage over B cells. However, there has been a long-lasting debate on whether Notch signaling is required for the maintenance of adult HSCs, utilizing transgenic animals inactivating different components of the Notch signaling pathway in HSCs or niche cells. The aims of the current mini-review are to summarize the evidence that disapproves or supports such hypothesis and point at imperative questions waiting to be addressed; hence, some of the seemingly contradictory findings could be reconciled. We need to better delineate the Notch signaling events using biochemical assays to identify direct Notch targets within HSCs or niche cells in specific biological context. More importantly, we call for more elaborate studies that pertain to whether niche cell type (vascular endothelial cells or other stromal cell)-specific Notch ligands regulate the differentiation of T cells in solid tumors during the progression of T-lymphoblastic lymphoma (T-ALL) or chronic myelomonocytic leukemia (CMML). We believe that the investigation of vascular endothelial cells' or other stromal cell types' interaction with hematopoietic cells during homeostasis and stress can offer insights toward specific and effective Notch-related therapeutics.

Expression and localisation of vascular ribonucleases in endothelial cells

2011 ◽  
Vol 105 (02) ◽  
pp. 345-355 ◽  
Author(s):  
Sara Dadkhahi ◽  
Julia Gansler ◽  
Mona Saffarzadeh ◽  
Aya Shibamiyama ◽  
Nicolé Kral ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Immediate Release ◽  
Vascular Endothelial ◽  
Short Term ◽  
Extracellular Rna ◽  
Cell Responses ◽  
Umbilical Vein Endothelial Cells

SummaryThe functions of extracellular RNA in the vascular system as new procoagulatory and permeability-increasing factor in vivoand in vitrowere shown to be counteracted by pancreatic type RNase1. Based on the identification of RNase1 in plasma and serum, it is proposed that the enzyme is expressed by vascular cells to contribute in the regulation of extracellular RNA. It is demonstrated that RNase1 and RNase5 (also termed angiogenin) were differentially expressed in various types of endothelial cells, whereby human umbilical vein endothelial cells (HUVEC) expressed and released the highest concentration of active RNase1. Expression and release of RNase5 were similar in all types of endothelial cells tested. Both RNases were constitutively produced and secreted, whereby a portion of RNase1, but not RNase5, was stored in Weibel-Palade bodies, co-localising with von Willlebrand factor and P-selectin. Accordingly, immediate release of RNase1 from these granules was demonstrated in vitroand in vivousing Weibel-Palade body exocytosis-inducing agents. Additionally, extracellular RNA or poly:IC (but not DNA) induced this short-term release of RNase1. Our results indicate that vascular RNase1 and RNase5 are mainly produced by vascular endothelial cells and can serve, depending on the vascular bed, different functions in vascular homeostasis and endothelial cell responses.

scholarly journals Dual Role of Jam3b in Early Hematopoietic and Vascular Development

2019 ◽  
Author(s):  
Isao Kobayashi ◽  
Jingjing Kobayashi-Sun ◽  
Yuto Hirakawa ◽  
Madoka Ouchi ◽  
Koyuki Yasuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Signaling Cascade ◽  
Vascular Endothelial ◽  
Lateral Plate ◽  
Hematopoietic Stem

AbstractIn order to efficiently derive hematopoietic stem cells (HSCs) from pluripotent precursors, it is crucial to understand how mesodermal cells acquire hematopoietic or endothelial identity due to their close developmental connection. Although Npas4 has been recently identified as a conserved master regulator of hemato-vascular development, the molecular mechanisms underlying the cell fate divergence between hematopoietic and vascular endothelial cells are still unclear. Here, we show in zebrafish that the divergence of hematopoietic and vascular endothelial cells in mesodermal cells is regulated by Junctional adhesion molecule 3b (Jam3b) via two independent signaling pathways. Mutation of jam3b led to the reduction of npas4l expression in the posterior lateral plate mesoderm and defect of both hematopoietic and vascular development. Mechanistically, we uncover that Jam3b promotes endothelial specification by regulating npas4l expression through the repression of the Rap1a-Erk signaling cascade. Jam3b subsequently promotes hematopoietic development including HSCs by regulating lrrc15 expression in endothelial precursors through the activation of an integrin-dependent signaling cascade. Our data provide insight into the divergent mechanisms for instructing hematopoietic or vascular fates from mesodermal cells.

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