Neural crest cell-derived VEGF promotes embryonic jaw extension

Jaw morphogenesis depends on the growth of Meckel’s cartilage during embryogenesis. However, the cell types and signals that promote chondrocyte proliferation for Meckel’s cartilage growth are poorly defined. Here we show that neural crest cells (NCCs) and their derivatives provide an essential source of the vascular endothelial growth factor (VEGF) to enhance jaw vascularization and stabilize the major mandibular artery. We further show in two independent mouse models that blood vessels promote Meckel’s cartilage extension. Coculture experiments of arterial tissue with NCCs or chondrocytes demonstrated that NCC-derived VEGF promotes blood vessel growth and that blood vessels secrete factors to instruct chondrocyte proliferation. Computed tomography and X-ray scans of patients with hemifacial microsomia also showed that jaw hypoplasia correlates with mandibular artery dysgenesis. We conclude that cranial NCCs and their derivatives provide an essential source of VEGF to support blood vessel growth in the developing jaw, which in turn is essential for normal chondrocyte proliferation, and therefore jaw extension.

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The effects of embryonic retinal neurons on neural crest cell differentiation into Schwann cells

Development ◽

10.1242/dev.109.4.925 ◽

1990 ◽

Vol 109 (4) ◽

pp. 925-934 ◽

Cited By ~ 1

Author(s):

L.C. Smith-Thomas ◽

A.R. Johnson ◽

J.W. Fawcett

Keyword(s):

Schwann Cell ◽

Neural Crest ◽

Schwann Cells ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Cell Types ◽

Cell Markers ◽

Ngf Receptor ◽

S 100 ◽

The Many

Amongst the many cell types that differentiate from migratory neural crest cells are the Schwann cells of the peripheral nervous system. While it has been demonstrated that Schwann cells will not fully differentiate unless in contact with neurons, the factors that cause neural crest cells to enter the differentiative pathway that leads to Schwann cells are unknown. In a previous paper (Development 105: 251, 1989), we have demonstrated that a proportion of morphologically undifferentiated neural crest cells express the Schwann cell markers 217c and NGF receptor, and later, as they acquire the bipolar morphology typical of Schwann cells in culture, express S-100 and laminin. In the present study, we have grown axons from embryonic retina on neural crest cultures to see whether this has an effect on the differentiation of neural crest cells into Schwann cells. After 4 to 6 days of co-culture, many more cells had acquired bipolar morphology and S-100 staining than in controls with no retinal explant, and most of these cells were within 200 microns of an axon, though not necessarily in contact with axons. However, the number of cells expressing the earliest Schwann cell markers 217c and NGF receptor was not affected by the presence of axons. We conclude that axons produce a factor, which is probably diffusible, and which makes immature Schwann cells differentiate. The factor does not, however, influence the entry of neural crest cells into the earliest stages of the Schwann cell differentiative pathway.

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Angiogenesis in Lymph Nodes Is a Critical Regulator of Immune Response and Lymphoma Growth

Frontiers in Immunology ◽

10.3389/fimmu.2020.591741 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lutz Menzel ◽

Uta E. Höpken ◽

Armin Rehm

Keyword(s):

Lymph Nodes ◽

Blood Vessels ◽

Vascular Remodeling ◽

B Cell Lymphoma ◽

Cell Types ◽

Blood Stream ◽

Disease Stage ◽

Angiogenic Growth Factors ◽

High Endothelial Venules ◽

Vessel Growth

Tumor-induced remodeling of the microenvironment in lymph nodes (LNs) includes the formation of blood vessels, which goes beyond the regulation of metabolism, and shaping a survival niche for tumor cells. In contrast to solid tumors, which primarily rely on neo-angiogenesis, hematopoietic malignancies usually grow within pre-vascularized autochthonous niches in secondary lymphatic organs or the bone marrow. The mechanisms of vascular remodeling in expanding LNs during infection-induced responses have been studied in more detail; in contrast, insights into the conditions of lymphoma growth and lodging remain enigmatic. Based on previous murine studies and clinical trials in human, we conclude that there is not a universal LN-specific angiogenic program applicable. Instead, signaling pathways that are tightly connected to autochthonous and infiltrating cell types contribute variably to LN vascular expansion. Inflammation related angiogenesis within LNs relies on dendritic cell derived pro-inflammatory cytokines stimulating vascular endothelial growth factor-A (VEGF-A) expression in fibroblastic reticular cells, which in turn triggers vessel growth. In high-grade B cell lymphoma, angiogenesis correlates with poor prognosis. Lymphoma cells immigrate and grow in LNs and provide pro-angiogenic growth factors themselves. In contrast to infectious stimuli that impact on LN vasculature, they do not trigger the typical inflammatory and hypoxia-related stroma-remodeling cascade. Blood vessels in LNs are unique in selective recruitment of lymphocytes via high endothelial venules (HEVs). The dissemination routes of neoplastic lymphocytes are usually disease stage dependent. Early seeding via the blood stream requires the expression of the homeostatic chemokine receptor CCR7 and of L-selectin, both cooperate to facilitate transmigration of tumor and also of protective tumor-reactive lymphocytes via HEV structures. In this view, the HEV route is not only relevant for lymphoma cell homing, but also for a continuous immunosurveillance. We envision that HEV functional and structural alterations during lymphomagenesis are not only key to vascular remodeling, but also impact on tumor cell accessibility when targeted by T cell–mediated immunotherapies.

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Misregulation of SDF1-CXCR4 Signaling Impairs Early Cardiac Neural Crest Cell Migration Leading to Conotruncal Defects

Circulation Research ◽

10.1161/circresaha.113.301333 ◽

2013 ◽

Vol 113 (5) ◽

pp. 505-516 ◽

Cited By ~ 52

Author(s):

Sophie Escot ◽

Cédrine Blavet ◽

Sonja Härtle ◽

Jean-Loup Duband ◽

Claire Fournier-Thibault

Keyword(s):

Neural Crest ◽

Molecular Mechanisms ◽

Heart Diseases ◽

Smooth Muscles ◽

Neural Crest Cell ◽

Cell Types ◽

Ventricular Septum ◽

Embryonic Cells ◽

Loss Of Function ◽

Cardiac Neural Crest

Rationale: Cardiac neural crest cells (NCs) contribute to heart morphogenesis by giving rise to a variety of cell types from mesenchyme of the outflow tract, ventricular septum, and semilunar valves to neurons of the cardiac ganglia and smooth muscles of the great arteries. Failure in cardiac NC development results in outflow and ventricular septation defects commonly observed in congenital heart diseases. Cardiac NCs derive from the vagal neural tube, which also gives rise to enteric NCs that colonize the gut; however, so far, molecular mechanisms segregating these 2 populations and driving cardiac NC migration toward the heart have remained elusive. Objective: Stromal-derived factor-1 (SDF1) is a chemokine that mediates oriented migration of multiple embryonic cells and mice deficient for Sdf1 or its receptors, Cxcr4 and Cxcr7 , exhibit ventricular septum defects, raising the possibility that SDF1 might selectively drive cardiac NC migration toward the heart via a chemotactic mechanism. Methods and Results : We show in the chick embryo that Sdf1 expression is tightly coordinated with the progression of cardiac NCs expressing Cxcr4 . Cxcr4 loss-of-function causes delayed migration and enhanced death of cardiac NCs, whereas Sdf1 misexpression results in their diversion from their normal pathway, indicating that SDF1 acts as a chemoattractant for cardiac NCs. These alterations of SDF1 signaling result in severe cardiovascular defects. Conclusions: These data identify Sdf1 and its receptor Cxcr4 as candidate genes responsible for cardiac congenital pathologies in human.

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Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

10.1101/2020.04.27.063792 ◽

2020 ◽

Cited By ~ 1

Author(s):

Arsheen M. Rajan ◽

Roger C. Ma ◽

Katrinka M. Kocha ◽

Dan J. Zhang ◽

Peng Huang

Keyword(s):

Extracellular Matrix ◽

Blood Vessel ◽

Blood Vessels ◽

Time Lapse ◽

Cell Types ◽

Dual Function ◽

Zebrafish Model ◽

Tissue Ischemia ◽

Genetic Ablation ◽

Collagen Genes

ABSTRACTBlood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts results in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.AUTHOR SUMMARYBlood vessels are essential to sustain life in humans. Defects in blood vessels can lead to serious diseases, such as hemorrhage, tissue ischemia, and stroke. However, how blood vessel stability is maintained by surrounding support cells is still poorly understood. Using the zebrafish model, we identify a new population of blood vessel associated cells termed perivascular fibroblasts, which originate from the sclerotome, an embryonic structure that is previously known to generate the skeleton of the animal. Perivascular fibroblasts are distinct from pericytes, a known population of blood vessel support cells. They become associated with blood vessels much earlier than pericytes and express several collagen genes, encoding main components of the extracellular matrix. Loss of perivascular fibroblasts or mutations in collagen genes result in fragile blood vessels prone to damage. Using cell tracing in live animals, we find that a subset of perivascular fibroblasts can differentiate into pericytes. Together, our work shows that perivascular fibroblasts play two important roles in maintaining blood vessel integrity. Perivascular fibroblasts secrete collagens to stabilize newly formed blood vessels and a sub-population of these cells also functions as precursors to generate pericytes to provide additional vascular support.

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The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

Development ◽

10.1242/dev.128.21.4127 ◽

2001 ◽

Vol 128 (21) ◽

pp. 4127-4138 ◽

Cited By ~ 9

Author(s):

Mirella Dottori ◽

Michael K. Gross ◽

Patricia Labosky ◽

Martyn Goulding

Keyword(s):

Transcription Factor ◽

Neural Crest ◽

Cell Fate ◽

Neural Tube ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Cell Types ◽

Winged Helix ◽

Multiple Cell ◽

Winged Helix Transcription Factor

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.

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Tissue Interactions in Neural Crest Cell Development and Disease

Science ◽

10.1126/science.1230717 ◽

2013 ◽

Vol 341 (6148) ◽

pp. 860-863 ◽

Cited By ~ 71

Author(s):

Yoshiko Takahashi ◽

Douglas Sipp ◽

Hideki Enomoto

Keyword(s):

Neural Crest ◽

Vascular System ◽

Neural Crest Cell ◽

Hirschsprung Disease ◽

Cell Types ◽

Microbial Pathogens ◽

Environmental Signals ◽

Tissue Interactions ◽

Migratory Cells ◽

Different Cell Types

The neural crest is a transient population of migratory cells in the embryo that gives rise to a wide variety of different cell types, including those of the peripheral nervous system. Dysfunction of neural crest cells (NCCs) is associated with multiple diseases, such as neuroblastoma and Hirschsprung disease. Recent studies have identified NCC behaviors during their migration and differentiation, with implications for their contributions to development and disease. Here, we describe how interactions between cells of the neural crest and lineages such as the vascular system, as well as those involving environmental signals and microbial pathogens, are critically important in determining the roles played by these cells.

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Neural crest lineage analysis: from past to future trajectory

Development ◽

10.1242/dev.193193 ◽

2020 ◽

Vol 147 (20) ◽

pp. dev193193 ◽

Cited By ~ 1

Author(s):

Weiyi Tang ◽

Marianne E. Bronner

Keyword(s):

Neural Crest ◽

Cell Fate ◽

Single Molecule ◽

Cell Lineage ◽

Neural Crest Cell ◽

Cell Types ◽

Lineage Tracing ◽

Migration Routes ◽

Developmental Potential ◽

Lineage Analysis

ABSTRACTSince its discovery 150 years ago, the neural crest has intrigued investigators owing to its remarkable developmental potential and extensive migratory ability. Cell lineage analysis has been an essential tool for exploring neural crest cell fate and migration routes. By marking progenitor cells, one can observe their subsequent locations and the cell types into which they differentiate. Here, we review major discoveries in neural crest lineage tracing from a historical perspective. We discuss how advancing technologies have refined lineage-tracing studies, and how clonal analysis can be applied to questions regarding multipotency. We also highlight how effective progenitor cell tracing, when combined with recently developed molecular and imaging tools, such as single-cell transcriptomics, single-molecule fluorescence in situ hybridization and high-resolution imaging, can extend the scope of neural crest lineage studies beyond development to regeneration and cancer initiation.

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The neural crest stem cells: control of neural crest cell fate and plasticity by endothelin-3

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652001000400007 ◽

2001 ◽

Vol 73 (4) ◽

pp. 533-545 ◽

Cited By ~ 16

Author(s):

ELISABETH DUPIN ◽

CARLA REAL ◽

NICOLE LeDOUARIN

Keyword(s):

Stem Cells ◽

Neural Crest ◽

Cell Fate ◽

Neural Crest Cell ◽

Cell Types ◽

The Body ◽

Neural Crest Stem Cells ◽

Environmental Signals

How the considerable diversity of neural crest (NC)-derived cell types arises in the vertebrate embryo has long been a key question in developmental biology. The pluripotency and plasticity of differentiation of the NC cell population has been fully documented and it is well-established that environmental cues play an important role in patterning the NC derivatives throughout the body. Over the past decade, in vivo and in vitro cellular approaches have unravelled the differentiation potentialities of single NC cells and led to the discovery of NC stem cells. Although it is clear that the final fate of individual cells is in agreement with their final position within the embryo, it has to be stressed that the NC cells that reach target sites are pluripotent and further restrictions occur only late in development. It is therefore a heterogenous collection of cells that is submitted to local environmental signals in the various NC-derived structures. Several factors were thus identified which favor the development of subsets of NC-derived cells in vitro. Moreover, the strategy of gene targeting in mouse has led at identifying new molecules able to control one or several aspects of NC cell differentiation in vivo. Endothelin peptides (and endothelin receptors) are among those. The conjunction of recent data obtained in mouse and avian embryos and reviewed here contributes to a better understanding of the action of the endothelin signaling pathway in the emergence and stability of NC-derived cell phenotypes.

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Single cell RNA analysis of trunk neural crest cells in zebrafish identifies pre-migratory populations expressing markers of differentiated derivatives

10.1101/2020.12.24.424338 ◽

2020 ◽

Author(s):

Ezra Lencer ◽

Rytis Prekeris ◽

Kristin Bruk Artinger

Keyword(s):

Neural Crest ◽

Single Cell ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Cell Types ◽

Vertebrate Development ◽

Multiple Traits ◽

Transcriptional Changes ◽

Trunk Neural Crest ◽

Crest Cell

AbstractThe neural crest is a migratory population of stem-like cells that contribute to multiple traits including the bones of the skull, peripheral nervous system, and pigment. How neural crest cells differentiate into diverse cell types is a fundamental question in the study of vertebrate biology. Here, we use single cell RNA sequencing to characterize transcriptional changes associated with neural crest cell development in the zebrafish trunk during the early stages of migration. We show that neural crest cells are transcriptionally diverse, and identify pre-migratory populations already expressing genes associated with differentiated derivatives. Further, we identify a population of Rohon-Beard neurons that are shown to be sources of Fgf signaling in the zebrafish trunk. The data presented identify novel genetic markers for multiple trunk neural crest cell populations and Rohon-Beard neurons providing insight into previously uncharacterized genes critical for vertebrate development.

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Building Blood Vessels—One Rho GTPase at a Time

Cells ◽

10.3390/cells8060545 ◽

2019 ◽

Vol 8 (6) ◽

pp. 545 ◽

Cited By ~ 10

Author(s):

Haley Rose Barlow ◽

Ondine Cleaver

Keyword(s):

Blood Vessels ◽

Rho Gtpases ◽

Cell Biology ◽

Rho Gtpase ◽

Building Blocks ◽

Cell Types ◽

Small Gtpases ◽

Diffusion Limit ◽

Vessel Growth ◽

Relative Specificity

Blood vessels are required for the survival of any organism larger than the oxygen diffusion limit. Blood vessel formation is a tightly regulated event and vessel growth or changes in permeability are linked to a number of diseases. Elucidating the cell biology of endothelial cells (ECs), which are the building blocks of blood vessels, is thus critical to our understanding of vascular biology and to the development of vascular-targeted disease treatments. Small GTPases of the Rho GTPase family are known to regulate several processes critical for EC growth and maintenance. In fact, many of the 21 Rho GTPases in mammals are known to regulate EC junctional remodeling, cell shape changes, and other processes. Rho GTPases are thus an attractive target for disease treatments, as they often have unique functions in specific vascular cell types. In fact, some Rho GTPases are even expressed with relative specificity in diseased vessels. Interestingly, many Rho GTPases are understudied in ECs, despite their known expression in either developing or mature vessels, suggesting an even greater wealth of knowledge yet to be gleaned from these complex signaling pathways. This review aims to provide an overview of Rho GTPase signaling contributions to EC vasculogenesis, angiogenesis, and mature vessel barrier function. A particular emphasis is placed on so-called “alternative” Rho GTPases, as they are largely understudied despite their likely important contributions to EC biology.

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