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The Anatomical Record Nov 2002Epithelial-mesenchymal transitions (EMTs) are well known processes in which new mesenchyme is locally generated from epithelia. During the development of the vertebrate... (Review)
Review
Epithelial-mesenchymal transitions (EMTs) are well known processes in which new mesenchyme is locally generated from epithelia. During the development of the vertebrate embryo, EMTs are a source of mesenchyme in diverse places and stages through embryonic morphogenesis, especially in mesodermal domains. In the present work we consider the embryo as a two-state system in which epithelium and mesenchyme represent the stable and unstable states, respectively. We think that a pattern of recurrent oscillations between the plasticity and exploratory behaviour of the mesenchyme and the stability of the epithelia can be recognized in the embryogenesis of vertebrates and, probably, in most tripoblastic Metazoans. Mesoderm, in particular, might be regarded as a cell layer able to oscillate between epithelial and mesenchymal states. The cellular and molecular mechanisms that enable these recurrent oscillations between stable (epithelial) and unstable (mesenchymal) states during embryogenesis provide the mesoderm with a large plasticity, an extended potential for innovation, and a better control of the three-dimensional (3D) body organization. In this scenario, it is conceivable that the origin of the mesoderm itself might be related to ancestral mechanisms regulating cell adhesion and detachment. We conclude that EMTs played a key role in the evolution of Metazoans, and are involved in the pathological and reparative processes of adult organisms.
Topics: Animals; Biological Evolution; Embryonic Induction; Embryonic and Fetal Development; Epithelial Cells; Epithelium; Mesoderm; Morphogenesis; Origin of Life
PubMed: 12382329
DOI: 10.1002/ar.10165 -
Cellular and Molecular Life Sciences :... Sep 2008Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied... (Review)
Review
Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis.
Topics: Animals; Cell Differentiation; Cell Lineage; Humans; Mesoderm; Signal Transduction; Stem Cells; Wnt Proteins
PubMed: 18528633
DOI: 10.1007/s00018-008-8042-1 -
Developmental Cell Oct 2020The interplay between pancreatic epithelium and the surrounding microenvironment is pivotal for pancreas formation and differentiation as well as adult organ...
The interplay between pancreatic epithelium and the surrounding microenvironment is pivotal for pancreas formation and differentiation as well as adult organ homeostasis. The mesenchyme is the main component of the embryonic pancreatic microenvironment, yet its cellular identity is broadly defined, and whether it comprises functionally distinct cell subsets is not known. Using genetic lineage tracing, transcriptome, and functional studies, we identified mesenchymal populations with different roles during pancreatic development. Moreover, we showed that Pbx transcription factors act within the mouse pancreatic mesenchyme to define a pro-endocrine specialized niche. Pbx directs differentiation of endocrine progenitors into insulin- and glucagon-positive cells through non-cell-autonomous regulation of ECM-integrin interactions and soluble molecules. Next, we measured functional conservation between mouse and human pancreatic mesenchyme by testing identified mesenchymal factors in an iPSC-based differentiation model. Our findings provide insights into how lineage-specific crosstalk between epithelium and neighboring mesenchymal cells underpin the generation of different pancreatic cell types.
Topics: Animals; Cell Differentiation; Endocrine System; Epithelium; Gene Expression Regulation, Developmental; Humans; Mesenchymal Stem Cells; Mesoderm; Mice, Transgenic; Organogenesis; Pancreas
PubMed: 32857951
DOI: 10.1016/j.devcel.2020.08.003 -
Disease Models & Mechanisms Mar 2019Auditory bulla cavitation defects are a cause of otitis media, but the normal cellular pattern of bulla mesenchyme regression and its failure are not well understood. In...
Auditory bulla cavitation defects are a cause of otitis media, but the normal cellular pattern of bulla mesenchyme regression and its failure are not well understood. In mice, neural-crest-derived mesenchyme occupies the bulla from embryonic day 17.5 (E17.5) to postnatal day 11 (P11) and then regresses to form the adult air-filled bulla cavity. We report that bulla mesenchyme is bordered by a single layer of non-ciliated epithelium characterized by interdigitating cells with desmosome cell junctions and a basal lamina, and by gene expression and laminin staining of the basal lamina. At P11-P12, the mesenchyme shrinks: mesenchyme-associated epithelium shortens, and mesenchymal cells and extracellular matrix collagen fibrils condense, culminating in the formation of cochlea promontory mucosa bordered by compact non-ciliated epithelial cells. is a candidate disease gene in human chronic otitis media with effusion and we report that a bulla cavitation defect initiates the pathogenesis of otitis media in the established mouse model ( ). Persistent mesenchyme in bullae has limited mesenchymal cell condensation, fibrosis and hyperplasia of the mesenchyme-associated epithelium. Subsequent modification forms fibrous adhesions that link the mucosa and the tympanic membrane, and this is accompanied by dystrophic mineralization and accumulation of serous effusion in the bulla cavity. Mouse models of bulla cavitation defects are important because their study in humans is limited to post-mortem samples. This work indicates new diagnostic criteria for this otitis media aetiology in humans, and the prospects of studying the molecular mechanisms of murine bulla cavitation in organ culture.
Topics: Animals; Animals, Newborn; Chronic Disease; Disease Models, Animal; Ear, Middle; Epithelium; F-Box Proteins; Female; MDS1 and EVI1 Complex Locus Protein; Male; Mesoderm; Mice, Inbred C57BL; Otitis Media; Proto-Oncogene Proteins c-bcl-6; Snail Family Transcription Factors; Time Factors; Tissue Adhesions
PubMed: 30898767
DOI: 10.1242/dmm.038315 -
Journal of Anatomy Mar 2023Somites are transient structures derived from the pre-somitic mesoderm (PSM), involving mesenchyme-to-epithelial transition (MET) where the cells change their shape and...
Somites are transient structures derived from the pre-somitic mesoderm (PSM), involving mesenchyme-to-epithelial transition (MET) where the cells change their shape and polarize. Using Scanning electron microscopy (SEM), immunocytochemistry and confocal microscopy, we study the progression of these events along the tail-to-head axis of the embryo, which mirrors the progression of somitogenesis (younger cells located more caudally). SEM revealed that PSM epithelialization is a gradual process, which begins much earlier than previously thought, starting with the dorsalmost cells, then the medial ones, and then, simultaneously, the ventral and lateral cells, before a somite fully separates from the PSM. The core (internal) cells of the PSM and somites never epithelialize, which suggests that the core cells could be 'trapped' within the somitocoele after cells at the surfaces of the PSM undergo MET. Three-dimensional imaging of the distribution of the cell polarity markers PKCζ, PAR3, ZO1, the Golgi marker GM130 and the apical marker N-cadherin reveal that the pattern of polarization is distinctive for each marker and for each surface of the PSM, but the order of these events is not the same as the progression of cell elongation. These observations challenge some assumptions underlying existing models of somite formation.
Topics: Somites; Mesoderm; Morphogenesis; Cadherins; Embryonic Development
PubMed: 36423208
DOI: 10.1111/joa.13791 -
British Journal of Cancer Nov 2008Recent evidence has demonstrated that endothelial-to-mesenchymal transition (EndMT) may have a significant role in a number of diseases. Although EndMT has been... (Review)
Review
Recent evidence has demonstrated that endothelial-to-mesenchymal transition (EndMT) may have a significant role in a number of diseases. Although EndMT has been previously studied as a critical process in heart development, it is now clear that EndMT can also occur postnatally in various pathologic settings, including cancer and cardiac fibrosis. During EndMT, resident endothelial cells delaminate from an organised cell layer and acquire a mesenchymal phenotype characterised by loss of cell-cell junctions, loss of endothelial markers, gain of mesenchymal markers, and acquisition of invasive and migratory properties. Endothelial-to-mesenchymal transition -derived cells are believed to function as fibroblasts in damaged tissue, and may therefore have an important role in tissue remodelling and fibrosis. In tumours, EndMT is an important source of cancer-associated fibroblasts (CAFs), which are known to facilitate tumour progression in several ways. These new findings suggest that targeting EndMT may be a novel therapeutic strategy, which is broadly applicable not only to cancer but also to various other disease states.
Topics: Animals; Cell Differentiation; Disease Progression; Endothelial Cells; Fibroblasts; Fibrosis; Heart; Humans; Mesoderm; Myocardium; Neoplasms; Neovascularization, Physiologic; Signal Transduction
PubMed: 18797460
DOI: 10.1038/sj.bjc.6604662 -
Scientific Reports May 2015Odontogenesis is accomplished by reciprocal signaling between the epithelial and mesenchymal compartments. It is generally accepted that the inductive mesenchyme is...
Odontogenesis is accomplished by reciprocal signaling between the epithelial and mesenchymal compartments. It is generally accepted that the inductive mesenchyme is capable of inducing the odontogenic commitment of both dental and non-dental epithelial cells. However, the duration of this signal in the developing dental mesenchyme and whether adult dental pulp tissue maintains its inductive capability remain unclear. This study investigated the contribution of growth factors to regulating the inductive potential of the dental mesenchyme. Human oral epithelial cells (OEs) were co-cultured with either human dental mesenchymal/papilla cells (FDPCs) or human dental pulp cells (ADPCs) under 2-dimensional or 3-dimensional conditions. Odontogenic-associated genes and proteins were detected by qPCR and immunofluorescence, respectively, and significant differences were observed between the two co-culture systems. The BMP7 and EREG expression levels in FDPCs were significantly higher than in ADPCs, as indicated by human growth factor PCR arrays and immunofluorescence analyses. OEs co-cultured with ADPCs supplemented with BMP7 and EREG expressed ameloblastic differentiation genes. Our study suggests that BMP7 and EREG expression in late bell-stage human dental papilla contributes to the inductive potential of dental mesenchyme. Furthermore, adult dental pulp cells supplemented with these two growth factors re-established the inductive potential of postnatal dental pulp tissue.
Topics: Amelogenin; Bone Morphogenetic Protein 7; Cell Culture Techniques; Cell Differentiation; Cluster Analysis; Coculture Techniques; Dental Enamel Proteins; Dental Papilla; Dental Pulp; Epiregulin; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Mesoderm; Odontogenesis; PAX9 Transcription Factor
PubMed: 25952286
DOI: 10.1038/srep09903 -
Minerva Chirurgica Oct 2009Pancreatic cancer (PC) is an aggressive malignancy with one of the worst outcomes among all cancers. It is the fourth leading cause of cancer death in the United States... (Review)
Review
Pancreatic cancer (PC) is an aggressive malignancy with one of the worst outcomes among all cancers. It is the fourth leading cause of cancer death in the United States with a very low five-year survival rate. The high mortality of PC could, in part, be due to their drug resistance characteristics and high propensity for metastasis. Recently, cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells, which shares molecular characteristics with CSCs, have been believed to play critical roles in drug resistance and cancer metastasis as demonstrated in several human malignancies including PC. Thus, the discovery of molecular knowledge of drug resistance and metastasis in relation to CSCs and EMT in PC is becoming an important area of research, and such knowledge is likely to be helpful in the discovery of newer drugs as well as designing novel therapeutic strategies for the treatment of PC with better outcome. In this brief review, we will summarize the current knowledge regarding the CSCs and EMT in the context of drug resistance and metastasis in PC, the molecular events occurring in CSCs and EMT, and the design of novel therapeutic strategies targeting CSCs and EMT-type cells to increase drug sensitivity and suppression of metastasis toward better treatment outcome of patients diagnosed with PC.
Topics: Animals; Drug Resistance, Neoplasm; Epithelial Cells; Humans; Mesoderm; Neoplasm Metastasis; Neoplastic Stem Cells; Pancreatic Neoplasms
PubMed: 19859039
DOI: No ID Found -
Transplantation Reviews (Orlando, Fla.) Oct 2008Mesenchymal stromal cells (MSCs) originally isolated from bone marrow have been derived from almost every tissue in the body. These multipotent cells can be... (Review)
Review
Mesenchymal stromal cells (MSCs) originally isolated from bone marrow have been derived from almost every tissue in the body. These multipotent cells can be differentiated in vitro and in vivo into various cell types of mesenchymal origin, such as bone, fat, and cartilage. Furthermore, under some experimental conditions, these cells can differentiate into a wider variety of cell types. Upon systemic administration, ex vivo expanded MSCs preferentially home to damaged tissues and participate in regeneration processes through their diverse biological properties. In vitro and in vivo data suggest that MSCs have low inherent immunogenicity and modulate/suppress immunologic responses through interactions with different immune cells. Ease of isolation and ex vivo expansion of MSCs, combined with their intriguing differentiation and immunomodulatory potential, and their impressive record of safety in clinical trials make these cells prime candidates for cellular therapy. Mesenchymal stromal cells derived from bone marrow are currently being evaluated for a wide range of clinical applications including for treatment of immune dysregulation disorders such as acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In the future, MSCs might potentially provide novel therapeutic options for treatment/prevention of rejection and/or repair of organ allografts through their multifaceted properties.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Mesoderm; Organ Transplantation; Stromal Cells
PubMed: 18656340
DOI: 10.1016/j.trre.2008.05.002 -
The International Journal of... 2005In vertebrates, the eye is an ectodermal compound structure associating neurectodermal and placodal anlagen. In addition, it benefits early on from a mesenchymal... (Review)
Review
In vertebrates, the eye is an ectodermal compound structure associating neurectodermal and placodal anlagen. In addition, it benefits early on from a mesenchymal ectoderm-derived component, the neural crest. In this respect, the construction of chimeras between quail and chick has been a turning point, instrumental in appraising the contribution of the cephalic neural crest to the development of ocular and periocular structures. Given the variety of crest derivatives underscored in the developing eye, this study illustrates the fascinating ability of this unique structure to finely adapt its differentiation to microenvironmental cues. This analysis of neural crest cell contribution to ocular development emphasizes their paramount role to design the anterior segment of the eye, supply refracting media and contribute to the homeostasy of the anterior optic chamber.
Topics: Animals; Chick Embryo; Eye; Mesoderm; Neural Crest; Quail; Retinal Vessels; Transplantation Chimera
PubMed: 15906229
DOI: 10.1387/ijdb.041937sc