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Current Opinion in Cell Biology Oct 2012Immunity, embryogenesis and tissue repair rely heavily on cell migration. Cells can be seen migrating as individuals or large groups. In the latter case, collectiveness... (Review)
Review
Immunity, embryogenesis and tissue repair rely heavily on cell migration. Cells can be seen migrating as individuals or large groups. In the latter case, collectiveness emerges via cell-cell interactions. In migratory epithelial cell sheets, classic Cadherins are critical to maintain tissue integrity, to promote coordination and establish cell polarity. However, recent evidence indicates that mesenchymal cells, migrating in streams such as neural crest or cancer cells, also exhibit collective migration. Here we will explore the idea that Cadherins play an essential role during collective migration of mesenchymal cells.
Topics: Animals; Cadherins; Cell Adhesion; Cell Movement; Cell Polarity; Mesoderm; Neural Crest
PubMed: 22944726
DOI: 10.1016/j.ceb.2012.08.002 -
Journal of Cell Science. Supplement 1988Mesenchyme tissue: cells, matrix and soluble factors, influence the morphogenesis, proliferation and differentiation of a variety of embryonic epithelia, e.g. in the... (Review)
Review
Mesenchyme tissue: cells, matrix and soluble factors, influence the morphogenesis, proliferation and differentiation of a variety of embryonic epithelia, e.g. in the tooth, skin, mammary and salivary glands. Mesenchyme derivatives also 'maintain' adult epithelia, e.g. the local proliferation rate and cytokeratin composition of oral mucosa. Abnormalities in such epithelial-mesenchymal interactions lead to a variety of pathologies such as premalignant lesions, e.g. leukoplakia, tumours and psoriasis, whilst therapeutic manipulation of such interactions can prevent the exfoliation of dental implants. In all of these systems it is critical to understand, at the cellular and molecular levels, how the mesenchyme signals to the epithelium and how the latter processes and responds to such signals. We have investigated such questions using the developing embryonic palate both as a model system and as an important organ: failure of mesenchymal signalling leads to the common and distressing birth defect of cleft palate. Bilateral palatal shelves arise from the maxillary processes of embryonic day 11 (E11) mice, grow initially vertically down the sides of the tongue, elevate on E13.8 to a horizontal position above the dorsum of the tongue and fuse with each other in the midline on E14. The medial edge epithelia of each shelf fuse with each other to form a midline epithelial seam, suprabasal cells die, and the basal (stem) cells synthesize extracellular matrix molecules and turn into mesenchymal cells. Simultaneously the oral epithelia differentiate into stratified squamous cells and the nasal epithelia into pseudostratified ciliated columnar cells. Oral, medial and nasal epithelial differentiation is specified by the underlying mesenchyme in vivo and in vitro. Signalling involves a bifurcating action of a combination of soluble growth factors e.g. TGF-alpha, TGF-beta, PDGF and FGF on palatal epithelia and mesenchyme. These factors stimulate the synthesis of specific extracellular matrix molecules by palate mesenchyme cells, and the appearance of receptors for such molecules on epithelial cells. In this way, a combination of mesenchymal soluble factors and extracellular matrix molecules direct palatal epithelial differentiation. These signals act on epithelial basal (stem) cells, causing them to synthesize unique proteins, which may direct subsequent differentiation of daughter cells. In the most extreme example, namely the medial edge epithelia, these signals result in the basal epithelial cells transforming into mesenchymal cells, thus demonstrating that they are indeed multipotential stem cells.
Topics: Animals; Epithelium; Extracellular Matrix; Growth Substances; Mammals; Mesoderm; Mice; Morphogenesis; Palate; Stem Cells
PubMed: 3077937
DOI: 10.1242/jcs.1988.supplement_10.15 -
Developmental Biology Apr 2011Urinary tract morphogenesis requires subdivision of the ureteric bud (UB) into the intra-renal collecting system and the extra-renal ureter, by responding to signals in...
Urinary tract morphogenesis requires subdivision of the ureteric bud (UB) into the intra-renal collecting system and the extra-renal ureter, by responding to signals in its surrounding mesenchyme. BMP4 is a mesenchymal regulator promoting ureter development, while GREM1 is necessary to negatively regulate BMP4 activity to induce UB branching. However, the mechanisms that regulate the GREM1-BMP4 signaling are unknown. Previous studies have shown that Six1-deficient mice lack kidneys, but form ureters. Here, we show that the tip cells of Six1(-/-) UB fail to form an ampulla for branching. Instead, the UB elongates within Tbx18- and Bmp4-expressing mesenchyme. We find that the expression of Grem1 in the metanephric mesenchyme (MM) is Six1-dependent. Treatment of Six1(-/-) kidney rudiments with GREM1 protein restores ampulla formation and branching morphogenesis. Furthermore, we demonstrate that genetic reduction of BMP4 levels in Six1(-/-) (Six1(-/-); Bmp4(+/-)) embryos restores urinary tract morphogenesis and kidney formation. This study uncovers an essential function for Six1 in the MM as an upstream regulator of Grem1 in initiating branching morphogenesis.
Topics: Animals; Bone Morphogenetic Protein 4; Embryo, Mammalian; Gene Dosage; Gene Expression Regulation, Developmental; Gene Silencing; Glial Cell Line-Derived Neurotrophic Factor; Homeodomain Proteins; Intercellular Signaling Peptides and Proteins; Kidney; Mesoderm; Mice; Morphogenesis; Organogenesis; Recombinant Proteins; T-Box Domain Proteins; Up-Regulation; Ureter; Wnt Proteins
PubMed: 21281623
DOI: 10.1016/j.ydbio.2011.01.027 -
Toxicologic Pathology Aug 2016In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165...
In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165 cases of mesenchyme-related tumors and nephroblastomas of the rat kidney were reexamined from the National Toxicology Program (NTP) Archives. This survey demonstrated that renal mesenchymal tumor (RMT) was the most common spontaneous nonepithelial tumor in the rat kidney, also occurring more frequently in the NTP studies than nephroblastoma. Renal sarcoma was a distinct but very rare tumor entity, representing a malignant, monomorphous population of densely crowded, fibroblast-like cells, in which, unlike RMT, preexisting tubules did not persist. Nephroblastoma was characterized by early death of affected animals, suggesting an embryonal origin for this tumor type. Male and female rats were equally disposed to developing RMT, but most of the cases of nephroblastoma occurred in female rats and liposarcoma occurred mostly in male rats. This survey confirmed discrete histopathological and biological differences between the mesenchyme-related renal tumor types and between RMT and nephroblastoma. Statistical analysis also demonstrated a lack of any relationship of these renal tumor types to test article administration in the NTP data bank.
Topics: Animals; Female; Kidney Neoplasms; Male; Mesoderm; Rats; Surveys and Questionnaires
PubMed: 27169591
DOI: 10.1177/0192623316638960 -
Genesis (New York, N.Y. : 2000) Jan 2019Cranial neural crest cells (CNCCs) give rise to cranial mesenchyme (CM) that differentiates into the forebrain meningeal progenitors in the basolateral and apical...
Cranial neural crest cells (CNCCs) give rise to cranial mesenchyme (CM) that differentiates into the forebrain meningeal progenitors in the basolateral and apical regions of the head. This occurs in close proximity to the other CNCC-CM-derivatives, such as calvarial bone and dermal progenitors. We found active Wnt signaling transduction in the forebrain meningeal progenitors in basolateral and apical populations and in the non-meningeal CM preceding meningeal differentiation. Here, we dissect the source of Wnt ligand secretion and requirement of Wnt/β-catenin signaling for the lineage selection and early differentiation of the forebrain meninges. We find persistent canonical Wnt/β-catenin signal transduction in the meningeal progenitors in the absence of Wnt ligand secretion in the CM or surface ectoderm, suggesting additional sources of Wnts. Conditional mutants for Wntless and β-catenin in the CM showed that Wnt ligand secretion and Wnt/β-catenin signaling were dispensable for specification and proliferation of early meningeal progenitors. In the absence of β-catenin in the CM, we found diminished laminin matrix and meningeal hypoplasia, indicating a structural and trophic role of mesenchymal β-catenin signaling. This study shows that β-catenin signaling is required in the CM for maintenance and organization of the differentiated meningeal layers in the basolateral and apical populations of embryonic meninges.
Topics: Animals; Cell Lineage; Intracellular Signaling Peptides and Proteins; Meninges; Mesoderm; Mice; Prosencephalon; Receptors, G-Protein-Coupled; Wnt Signaling Pathway; beta Catenin
PubMed: 30615824
DOI: 10.1002/dvg.23279 -
Genesis (New York, N.Y. : 2000) Jun 2018Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds... (Review)
Review
Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme. A second topic of discussion is germ layers (including the neural crest) as emergent levels of organization in animal development and evolution that facilitated major developmental and evolutionary change. The third topic is gene networks, gene co-option, and the evolution of gene-signaling pathways as key to developmental and evolutionary transitions associated with the origin and evolution of the neural crest and neural crest cells.
Topics: Animals; Biological Evolution; Chick Embryo; Ectoderm; Germ Layers; Humans; Mesoderm; Neural Crest; Vertebrates
PubMed: 29637683
DOI: 10.1002/dvg.23103 -
PloS One 2013The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or...
The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium. This study examines the potential for Foxd1-positive cells of the kidney and lung to give rise to endothelial progenitors. We utilized immunofluorescence (IF) and fluorescence-activated cell sorting (FACS) to co-label Foxd1-expressing cells (including permanently lineage-tagged cells) with endothelial markers in embryonic and postnatal mice. We also cultured FACsorted Foxd1-positive cells, performed in vitro endothelial cell tubulogenesis assays and examined for endocytosis of acetylated low-density lipoprotein (Ac-LDL), a functional assay for endothelial cells. Immunofluorescence and FACS revealed that a subset of Foxd1-positive cells from kidney and lung co-expressed endothelial cell markers throughout embryogenesis. In vitro, cultured embryonic Foxd1-positive cells were able to differentiate into tubular networks that expressed endothelial cell markers and were able to endocytose Ac-LDL. IF and FACS in both the kidney and lung revealed that lineage-tagged Foxd1-positive cells gave rise to a significant portion of the endothelium in postnatal mice. In the kidney, the stromal-derived cells gave rise to a portion of the peritubular capillary endothelium, but not of the glomerular or large vessel endothelium. These findings reveal the heterogeneity of endothelial cell lineages; moreover, Foxd1-positive mesenchymal cells of the developing kidney and lung are a source of endothelial progenitors that are likely critical to patterning the vasculature.
Topics: Animals; Biomarkers; Cell Differentiation; Cell Separation; Endothelial Progenitor Cells; Flow Cytometry; Forkhead Transcription Factors; Immunohistochemistry; Kidney; Lung; Mesoderm; Mice
PubMed: 23823180
DOI: 10.1371/journal.pone.0065993 -
The Journal of Cell Biology May 2007Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to...
Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1alpha. In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1alpha is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1alpha in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1alpha in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1alpha in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1alpha in early chondrogenesis and joint formation.
Topics: Animals; Cell Hypoxia; Chondrogenesis; Female; Hindlimb; Hypoxia-Inducible Factor 1, alpha Subunit; Joints; Mesoderm; Mice; Mice, Knockout; Pregnancy
PubMed: 17470636
DOI: 10.1083/jcb.200612023 -
Clinical and Experimental Dermatology Aug 2012
Topics: Adult; Fibroblasts; Humans; Immunohistochemistry; Mesoderm; Nails; Neprilysin
PubMed: 22369468
DOI: 10.1111/j.1365-2230.2011.04327.x -
Differentiation; Research in Biological... 2010Paracrine signalling from mesenchyme to epithelium plays a key role in regulating prostate organogenesis and it is important to identify the mesenchymally expressed...
Paracrine signalling from mesenchyme to epithelium plays a key role in regulating prostate organogenesis and it is important to identify the mesenchymally expressed molecules that regulate organ growth, though currently few such molecules are known. Tyrosine kinase signalling via EphB receptors has been characterised in many developmental processes, and EphB3 mRNA expression was detected in prostate inductive mesenchyme in previous gene profiling studies. This led us to examine the expression and function of EphrinB signalling in prostate development, to determine if EphrinB ligands might function as mesenchymal paracrine regulators of prostate growth. Using PCR, wholemount in situ hybridisation, and immunohistochemistry we examined the expression of EphB receptors and EphrinB ligands in rat prostate during development to determine which showed mesenchymal expression. EphB3 and EphrinB1 transcripts and proteins were expressed in the mesenchyme of developing prostate and in female urogenital mesenchyme and smooth muscle. The function of EphrinB signalling was examined using in vitro organ culture assays of ventral prostate (VP), which were treated with EphB3-Fc and EphrinB1-Fc proteins to inhibit or augment Ephrin signalling. Addition of recombinant EphB3-Fc resulted in a significant decrease in VP organ size, while recombinant EphrinB1-Fc resulted in a significant increase in VP organ size and epithelial proliferation. Additionally, EphrinB1-Fc reduced the degree of epithelial branching in VP organs and increased ductal tip size, though without disrupting normal differentiation. We have identified expression of EphrinB1 in prostatic mesenchyme and suggest that the EphrinB signalling system acts as a regulator of prostate growth. EphrinB-EphB signalling may function as an autocrine regulator of mesenchyme and/or as a paracrine regulator of epithelia.
Topics: Animals; Base Sequence; DNA Primers; Ephrin-B1; Immunohistochemistry; In Situ Hybridization; Ligands; Male; Mesoderm; Paraffin Embedding; Polymerase Chain Reaction; Prostate; RNA Probes; Rats; Rats, Wistar; Receptors, Eph Family; Signal Transduction
PubMed: 20633976
DOI: 10.1016/j.diff.2010.06.003