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Journal of Biochemistry Apr 1996Specific tissue interactions between epithelia and mesenchyme (or stroma), e.g., epithelial-mesenchymal (or -stromal) interactions mediate crucial aspects of normal... (Review)
Review
Specific tissue interactions between epithelia and mesenchyme (or stroma), e.g., epithelial-mesenchymal (or -stromal) interactions mediate crucial aspects of normal development and tissue regeneration. These events affect tissue induction, organogenesis, cell movement, and morphogenesis of multicellular structures. Extensive and diverse studies have established that hepatocyte growth factor (HGF), a ligand for the c-met protooncogene product of receptor tyrosine kinase, is a mesenchymal- or stromal-derived multipotent polypeptide which mediates epithelial-mesenchymal interactions. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues and organs, including the liver, kidney, lung, gut, mammary gland, tooth, skeletal system, etc. In adult tissues, HGF elicits a potent organotrophic function which supports regeneration of organs including the liver, kidney, and lung. In the brain, HGF is a new member of the family of neurotrophic factors. In neoplastic tissue, HGF is involved in tumor invasion and metastasis, through tumor-stromal interactions. While HGF was originally identified as a potent mitogen for mature hepatocytes, the biological functions of this factor reach far beyond the original identifications. Such being the case, use of HGF for purposes of therapeutics is being given increasing attention.
Topics: Animals; Cell Communication; Embryonic and Fetal Development; Epithelial Cells; Hepatocyte Growth Factor; Humans; Mesoderm; Morphogenesis; Regeneration
PubMed: 8743556
DOI: 10.1093/oxfordjournals.jbchem.a021283 -
EMBO Reports Aug 2022Development of vertebrate limbs and fins requires that tissue growth is directed outwards, away from the body. How such directed growth is achieved is a fascinating...
Development of vertebrate limbs and fins requires that tissue growth is directed outwards, away from the body. How such directed growth is achieved is a fascinating biological problem. For limb/fin formation and outgrowth, signaling between mesenchymal cells and the overlying epithelium is essential. In particular, the epithelium at the distal margin of the growing limb/fin bud, termed the apical ectodermal ridge (AER), promotes directed outgrowth of the underlying mesenchyme, e.g., by providing polarization cues for mesenchymal cell migration. Several classical signaling pathways, such as fibroblast growth factor (Fgf), hedgehog, and Wnt signaling, are involved in the regulation of the cellular events that shape the limb/fin bud (Iovine, 2007). In this issue of EMBO Reports, Carney and colleagues surprisingly find that the Slit-Robo pathway, which is best known for its function in axon guidance, regulates the polarity of developing zebrafish fins (Mahabaleshwar et al, 2007). Intriguingly, they identify an intricate back and forth of signals between the mesenchyme and the AER. Slit ligands derived from mesenchyme act on Robo receptors in the AER to stimulate the production of sphingosine-1-phosphate, which then acts back on the mesenchyme to regulate cell polarity and orientation.
Topics: Animals; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Limb Buds; Mesoderm; Morphogenesis; Zebrafish; Zebrafish Proteins
PubMed: 35836403
DOI: 10.15252/embr.202255563 -
Molecular and Cellular Biology May 2020The extensive array of basic helix-loop-helix (bHLH) transcription factors and their combinations as dimers underpin the diversity of molecular function required for...
The extensive array of basic helix-loop-helix (bHLH) transcription factors and their combinations as dimers underpin the diversity of molecular function required for cell type specification during embryogenesis. The bHLH factor TWIST1 plays pleiotropic roles during development. However, which combinations of TWIST1 dimers are involved and what impact each dimer imposes on the gene regulation network controlled by TWIST1 remain elusive. In this work, proteomic profiling of human TWIST1-expressing cell lines and transcriptome analysis of mouse cranial mesenchyme have revealed that TWIST1 homodimers and heterodimers with TCF3, TCF4, and TCF12 E-proteins are the predominant dimer combinations. Disease-causing mutations in TWIST1 can impact dimer formation or shift the balance of different types of TWIST1 dimers in the cell, which may underpin the defective differentiation of the craniofacial mesenchyme. Functional analyses of the loss and gain of TWIST1-E-protein dimer activity have revealed previously unappreciated roles in guiding lineage differentiation of embryonic stem cells: TWIST1-E-protein heterodimers activate the differentiation of mesoderm and neural crest cells, which is accompanied by the epithelial-to-mesenchymal transition. At the same time, TWIST1 homodimers maintain the stem cells in a progenitor state and block entry to the endoderm lineage.
Topics: Animals; Cell Differentiation; Cell Line; Dogs; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Developmental; Humans; Madin Darby Canine Kidney Cells; Mesoderm; Mice, Inbred C57BL; Mutation; Neural Crest; Nuclear Proteins; Protein Multimerization; Transcriptome; Twist-Related Protein 1
PubMed: 32179550
DOI: 10.1128/MCB.00663-19 -
Archives of Pathology & Laboratory... Oct 2006Hepatic mesenchymal hamartoma is a hamartomatous growth of mesenchymal tissue in the liver of uncertain etiology. It is a space-occupying lesion that can potentially... (Review)
Review
Hepatic mesenchymal hamartoma is a hamartomatous growth of mesenchymal tissue in the liver of uncertain etiology. It is a space-occupying lesion that can potentially compress adjacent organs resulting in various complications including death. Hepatic mesenchymal hamartoma is characterized by proliferation of variably myxomatous mesenchyme and malformed bile ducts. The differential diagnosis includes other pediatric hepatic masses. The diagnosis is typically made during infancy, and complete resection is invariably curative.
Topics: Bile Ducts; Diagnosis, Differential; Fetal Diseases; Fetal Therapies; Hamartoma; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Mesoderm; Suction
PubMed: 17090204
DOI: 10.5858/2006-130-1567-HMHASR -
Annual Review of Physiology 2011The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone... (Review)
Review
The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow-derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.
Topics: Animals; Biomarkers; Cell Differentiation; Epithelial-Mesenchymal Transition; Female; Hedgehog Proteins; Humans; Immunity, Innate; Intestines; Male; Mesenchymal Stem Cells; Mesoderm; Mice; Mucous Membrane; Myofibroblasts; Pericytes; Signal Transduction; Stromal Cells
PubMed: 21054163
DOI: 10.1146/annurev.physiol.70.113006.100646 -
Scientific Reports Jun 2015Mesenchyme is an embryonic precursor tissue that generates a range of structures in vertebrates including cartilage, bone, muscle, kidney, and the erythropoietic system....
Mesenchyme is an embryonic precursor tissue that generates a range of structures in vertebrates including cartilage, bone, muscle, kidney, and the erythropoietic system. Mesenchyme originates from both mesoderm and the neural crest, an ectodermal cell population, via an epithelial to mesenchymal transition (EMT). Because ectodermal and mesodermal mesenchyme can form in close proximity and give rise to similar derivatives, the embryonic origin of many mesenchyme-derived tissues is still unclear. Recent work using genetic lineage tracing methods have upended classical ideas about the contributions of mesodermal mesenchyme and neural crest to particular structures. Using similar strategies in the Mexican axolotl (Ambystoma mexicanum), and the South African clawed toad (Xenopus laevis), we traced the origins of fin mesenchyme and tail muscle in amphibians. Here we present evidence that fin mesenchyme and striated tail muscle in both animals are derived solely from mesoderm and not from neural crest. In the context of recent work in zebrafish, our experiments suggest that trunk neural crest cells in the last common ancestor of tetrapods and ray-finned fish lacked the ability to form ectomesenchyme and its derivatives.
Topics: Amphibians; Animals; Biomarkers; Epidermis; Larva; Mesoderm; Muscles; Neural Crest; Tail
PubMed: 26086331
DOI: 10.1038/srep11428 -
Development (Cambridge, England) Aug 2011The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are...
The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth.
Topics: Animals; Cell Proliferation; Female; Gastrointestinal Tract; Gene Expression Regulation, Developmental; Hedgehog Proteins; Male; Mesoderm; Mice; Mice, Knockout; Mice, Transgenic; Receptors, Notch; Signal Transduction
PubMed: 21750033
DOI: 10.1242/dev.066233 -
Developmental Biology Apr 1995The apical ectodermal ridge (AER) is a specialized thickening of the distal limb mesenchyme that has been demonstrated to support limb outgrowth and proper limb...
The apical ectodermal ridge (AER) is a specialized thickening of the distal limb mesenchyme that has been demonstrated to support limb outgrowth and proper limb development. The homeobox gene, Msx-1, is associated with the distal limb mesenchyme (progress zone) and its expression depends upon the presence of the AER in chick limbs. We demonstrate here that the expression of Msx-1 is dependent upon the limb ectoderm in the mouse, but that the inductive capacity of murine limb ectoderm is not restricted to the AER. Msx-1 can also be maintained in limb mesenchyme by the substitution of FGF 4 for the ectoderm; however, we see that local cell-cell interactions are required for high levels of expression. Disruption of cell-cell interactions in the limb mesenchyme results in a dramatic decrease in Msx-1 levels and a precocious expression of MyoD1, suggesting that the limb environment represses differentiation and promotes cell proliferation during early development. BMP 4 and FGF 2 can also maintain Msx-1 expression in limb mesenchyme as well as retinoic acid which is usually associated with polarizing activity in the early limb. Msx-2 expression does not appear to be dependent upon cell-cell interactions as measured in these experiments. Taken together, our data suggest that the expression of Msx-1, but not Msx-2, not only requires factors from the limb ectoderm, but also relies upon cues from local cell interactions and that the spatial distribution of inductive capacities in limb ectoderm differs between the avian and murine systems.
Topics: Animals; Base Sequence; Cell Communication; Cell Differentiation; Cells, Cultured; DNA, Complementary; Ectoderm; Extremities; Homeodomain Proteins; In Situ Hybridization; MSX1 Transcription Factor; Mesoderm; Mice; Molecular Sequence Data; Polymerase Chain Reaction; RNA; Transcription Factors
PubMed: 7537232
DOI: 10.1006/dbio.1995.1087 -
Cellular and Molecular Life Sciences :... Oct 2015The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and... (Review)
Review
The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.
Topics: Cell Communication; Cell Differentiation; Gastrointestinal Tract; Humans; Intestinal Mucosa; Mesoderm; Myocytes, Smooth Muscle; Signal Transduction; Transcription Factors
PubMed: 26126787
DOI: 10.1007/s00018-015-1975-2 -
Stem Cell Research & Therapy Jan 2019Human mesenchymal stem cells are a strong candidate for cell therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory...
BACKGROUND
Human mesenchymal stem cells are a strong candidate for cell therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory activity. Yet, their scarcity, limited expansion potential, and age-associated functional decline restrict the ability to consistently manufacture large numbers of safe and therapeutically effective mesenchymal stem cells for routine clinical applications. To overcome these limitations and advance stem cell treatments using mesenchymal stem cells, researchers have recently derived mesenchymal progenitors from human-induced pluripotent stem cells. Human-induced pluripotent stem cell-derived progenitors resemble adult mesenchymal stem cells in morphology, global gene expression, surface antigen profile, and multi-differentiation potential, but unlike adult mesenchymal stem cells, it can be produced in large numbers for every patient. For therapeutic applications, however, human-induced pluripotent stem cell-derived progenitors must be produced without animal-derived components (xeno-free) and in accordance with Good Manufacturing Practice guidelines.
METHODS
In the present study we investigate the effects of expanding mesodermal progenitor cells derived from two human-induced pluripotent stem cell lines in xeno-free medium supplemented with human platelet lysates and in a commercial high-performance Good Manufacturing Practice-compatible medium (Unison Medium).
RESULTS
The results show that long-term culture in xeno-free and Good Manufacturing Practice-compatible media somewhat affects the morphology, expansion potential, gene expression, and cytokine profile of human-induced pluripotent stem cell-derived progenitors but supports cell viability and maintenance of a mesenchymal phenotype equally well as medium supplemented with fetal bovine serum.
CONCLUSIONS
The findings support the potential to manufacture large numbers of clinical-grade human-induced pluripotent stem cell-derived mesenchymal progenitors for applications in personalized regenerative medicine.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Proliferation; Culture Media; Gene Expression Regulation, Developmental; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Mesoderm; Regenerative Medicine
PubMed: 30635059
DOI: 10.1186/s13287-018-1119-3