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Nature Reviews. Molecular Cell Biology Feb 2006Epithelial-mesenchymal transition is an indispensable mechanism during morphogenesis, as without mesenchymal cells, tissues and organs will never be formed. However,... (Review)
Review
Epithelial-mesenchymal transition is an indispensable mechanism during morphogenesis, as without mesenchymal cells, tissues and organs will never be formed. However, epithelial-cell plasticity, coupled to the transient or permanent formation of mesenchyme, goes far beyond the problem of cell-lineage segregation. Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
Topics: Animals; Cell Differentiation; Embryonic Development; Epithelial Cells; Gastrula; Heart Valves; Humans; Mesoderm; Mice; Neoplasms; Signal Transduction
PubMed: 16493418
DOI: 10.1038/nrm1835 -
Journal of Electron Microscopy 2003Tooth morphogenesis is a well-known developmental system related to epithelial-mesenchymal interactions. In mice, the dental epithelium has the potential to induce tooth...
Tooth morphogenesis is a well-known developmental system related to epithelial-mesenchymal interactions. In mice, the dental epithelium has the potential to induce tooth formation prior to the bud stage, whereas this potential shifts to the dental mesenchyme from the dental epithelium. The reaggregation of mesenchymal tissue leads to previous memories of individual cells being reset, which is useful for studying the predetermination of mesenchyme. Here, the mesenchyme was triturated into single cells after separation of the epithelium and the mesenchyme. These single cells were repelleted and combined with the epithelium. The reaggregated tooth was transplanted into a mice kidney capsule. In order to investigate the essential functions of both the dental epithelium and the dental mesenchyme regarding their mutual interaction, a reaggregation system was introduced using the late bud stage of the mouse first molar. Amelogenin expression was examined to confirm the cytodifferentiation in the reaggregated tooth. The results showed that a new tooth formed after reaggregating the dental mesenchyme. This tooth contained enamel, dentin, dentinal tubules and dental pulp. The inner enamel epithelium of the reaggregated tooth differentiated into ameloblasts. Immunohistochemistry for amelogenin was observed both in the ameloblasts and the enamel. However, the structure of the enamel was different from that of the normal tooth, with the thickness of the predentin becoming wider. These findings suggest that reaggregated dental mesenchyme cells can produce a tooth. The fate of dental epithelium was not affected by reaggregated dental mesenchyme, although the dental mesenchyme appears to lose the information from the dental epithelium.
Topics: Amelogenin; Animals; Cell Aggregation; Cell Differentiation; Dental Enamel Proteins; Epithelium; Mesoderm; Mice; Mice, Inbred ICR; Molar; Morphogenesis; Odontogenesis
PubMed: 14756244
DOI: 10.1093/jmicro/52.6.559 -
Developmental Dynamics : An Official... Dec 2017During murine kidney development, new cortical blood vessels form and pattern in cycles that coincide with cycles of collecting duct branching and the accompanying...
BACKGROUND
During murine kidney development, new cortical blood vessels form and pattern in cycles that coincide with cycles of collecting duct branching and the accompanying splitting of the cap mesenchyme (nephron progenitor cell populations that "cap" collecting duct ends). At no point in the patterning cycle do blood vessels enter the cap mesenchyme. We hypothesized that the exclusion of blood vessels from the cap mesenchyme may be controlled, at least in part, by an anti-angiogenic signal expressed by the cap mesenchyme cells.
RESULTS
We show that semaphorin-3f (Sema3f), a known anti-angiogenic factor, is expressed in cap mesenchymal cells and its receptor, neuropilin-2 (Nrp2), is expressed by newly forming blood vessels in the cortex of the developing kidney. We hypothesized that Sema3f/Nrp2 signaling excludes vessels from the cap mesenchyme. Genetic ablation of Sema3f and of Nrp2, however, failed to result in vessels invading the cap mesenchyme.
CONCLUSIONS
Despite complementary expression patterns, our data suggest that Sema3f and Nrp2 are dispensable for the exclusion of vessels from the cap mesenchyme during kidney development. These results should provoke additional experiments to ascertain the biological significance of Sema3f/Nrp2 expression in the developing kidney. Developmental Dynamics 246:1047-1056, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Gene Expression Regulation, Developmental; Kidney; Membrane Proteins; Mesoderm; Mice; Models, Biological; Neovascularization, Physiologic; Nerve Tissue Proteins; Neuropilin-2
PubMed: 28929539
DOI: 10.1002/dvdy.24592 -
Annual Review of Physiology 2004Classical experiments in embryology have shown that normal growth, morphogenetic patterning, and cellular differentiation in the developing lung depend on interactive... (Review)
Review
Classical experiments in embryology have shown that normal growth, morphogenetic patterning, and cellular differentiation in the developing lung depend on interactive signaling between the endodermal epithelium and mesenchyme derived from splanchnic mesoderm. These interactions are mediated by a myriad of diffusible factors that are precisely regulated in their temporal and spatial expression. In this review we first describe factors regulating formation of the embryonic foregut. We then discuss the experiments demonstrating the importance of tissue interactions in lung patterning and differentiation. Finally, we detail the roles that a few key signaling systems-fibroblast growth factors and their receptors, sonic hedgehog and Gli genes, Wnt genes and beta-catenin, and BMP4-play as mediators of epithelial-mesenchymal interactions in the developing lung.
Topics: Animals; Embryo, Mammalian; Embryonic and Fetal Development; Endoderm; Epithelium; Humans; Lung; Mesoderm
PubMed: 14977416
DOI: 10.1146/annurev.physiol.66.032102.135749 -
Biochemical Pharmacology Oct 2000Herein we discuss the factors that bring about the transformation of epithelial cells into cells of fibroblastic phenotype. This type of transformation, referred to as... (Review)
Review
Herein we discuss the factors that bring about the transformation of epithelial cells into cells of fibroblastic phenotype. This type of transformation, referred to as epithelium-to-mesenchyme transition (EMT), allows cells to dissociate from the epithelial tissue from which they originate and to migrate freely. EMT is therefore thought to play a fundamental role during the early steps of invasion and metastasis of carcinoma cells. Among biological agents which have been identified as inducers of EMT are a number of cytokines and extracellular matrix macromolecules. The coordinated changes in cell morphology, associated with the induction of cell motility and the disruption of intercellular junctions, are the consequence of a signaling cascade emanating from the plasma membrane and leading to changes in gene expression. Understanding the mechanisms regulating EMT of normal and transformed epithelial cells may offer new perspectives for designing therapies for the treatment of metastatic cancers of epithelial origin.
Topics: Animals; Cell Adhesion; Cell Movement; Epithelial Cells; Humans; Mesoderm; Signal Transduction
PubMed: 11007946
DOI: 10.1016/s0006-2952(00)00427-5 -
Seminars in Cell & Developmental Biology Aug 2019Pancreas organogenesis depends on proper interactions of endoderm-derived epithelial cells, which will form the exocrine and endocrine cells of the adult organ, with... (Review)
Review
Pancreas organogenesis depends on proper interactions of endoderm-derived epithelial cells, which will form the exocrine and endocrine cells of the adult organ, with their surrounding mesenchymal layer. Research on the role of pancreatic mesenchyme, pioneered by Golosow and Grobstein in the 1960's, revealed these cells regulate multiple events during pancreas development. Still, much is unknown regards the molecular basis of epithelial-mesenchymal interactions in this process. Here, we review in vivo and ex vivo approaches to study mesenchymal requirements for mammal pancreas organogenesis, and how gained knowledge is being translated toward the development of cell replacement therapy for diabetes.
Topics: Animals; Cell Differentiation; Humans; Mesoderm; Mice; Mice, Transgenic; Organogenesis; Pancreas
PubMed: 30172049
DOI: 10.1016/j.semcdb.2018.08.012 -
Developmental Dynamics : An Official... Dec 1999BMP-7 is a member of the BMP family of signaling molecules that are thought to play key roles in mediating inductive events during embryogenesis. In the present study...
BMP-7 is a member of the BMP family of signaling molecules that are thought to play key roles in mediating inductive events during embryogenesis. In the present study the possible roles of BMP-7 in mediating inductive events during the initiation phase of odontogenesis and mandibular morphogenesis were investigated. To do so, we have examined the effects of agarose beads soaked in recombinant BMP-7 on E11 mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme, and analyzed the patterns of expression of Bmp-7 in developing mouse and chick first branchial arches. Beads releasing BMP-7 induced a translucent zone, cellular proliferation, and expression of Msx-1, Msx-2, and Bmp-4 in molar-forming mesenchyme after 24 hr. The effects of BMP-7 on molar-forming mesenchyme are similar to the effects of BMP-4 and are consistent with their overlapping patterns of expression in the thickened epithelium of the early developing tooth buds, which is suggestive of cooperative and/or redundant roles of BMPs in mediating the inductive interactions during the early stages of odontogenesis. Our studies in the developing chick mandible showed that Bmp-7 is expressed in the mandibular epithelium. In the absence of mandibular epithelium, BMP-7 beads maintained cell proliferation and Msx expression in the medial mandibular mesenchyme and were able to induce cell proliferation, cell death, and Msx expression in the lateral chick mandibular mesenchyme. The effects of BMP-7 on the expression of Msx genes in lateral chick mandibular mesenchyme, although different from the effects of lateral mandibular epithelium, are similar to the effects of epithelium from the medial region where multiple Bmps are expressed. We also showed that laterally placed BMP-7 beads induced ectopic expression of Msx genes and changes in the development of posterior skeletal elements in the maxillary and mandibular arches. However, despite its proliferative effects on mandibular mesenchyme, BMP-7 did not support the directional outgrowth of the mandible. These observations suggest that epithelial-mesenchymal interactions in the medial region of the mandibular arch regulating directional outgrowth of the mandibular mesenchyme are mediated by cooperative interactions between BMPs and other growth factors. Our observations also indicated that EGF, another growth factor implicated in mediating epithelial-mesenchymal interactions in the initiation phase of odontogenesis and morphogenesis of the developing mandible, induces an extensive translucent zone and cellular proliferation in the E11 mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme. However, in contrast to BMPs, EGF did not induce Msx-1, Msx-2, and Bmp-4, but modulated the effects of BMPs on the expression of Msx-1 and Msx-2 in these mesenchymes. Our combined data suggest that BMP-7 is a component of the signaling network mediating epithelial-mesenchymal interactions during the initiation phase of odontogenesis and morphogenesis of the mandibular arch.
Topics: Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Cartilage, Articular; Cell Division; Chick Embryo; DNA-Binding Proteins; Epidermal Growth Factor; Epithelium; Gene Expression Regulation, Developmental; Homeodomain Proteins; MSX1 Transcription Factor; Mandible; Mesoderm; Mice; Morphogenesis; Odontogenesis; Tooth; Transcription Factors; Transforming Growth Factor beta
PubMed: 10633853
DOI: 10.1002/(SICI)1097-0177(199912)216:4/5<320::AID-DVDY2>3.0.CO;2-H -
The International Journal of... 2012Tooth development is controlled by reciprocal epithelial-mesenchymal interactions. Complete teeth can form when culturing and implanting re-associations between single...
Tooth development is controlled by reciprocal epithelial-mesenchymal interactions. Complete teeth can form when culturing and implanting re-associations between single embryonic dental epithelial and mesenchymal cells. Although epithelial histogenesis is clear, very little is known about cell diversity and patterning in the mesenchyme. The aim of this work was to compare the situation in engineered and developing teeth at similar developmental stages. To this end, the expression of cell surface markers in the mesenchyme was investigated by immunostaining in: 1) embryonic mouse molars at embryonic day 14, as the initial cell source for re-associations, 2) cultured cell re-associations just before their implantation and 3) cultured cell re-associations implanted for two weeks. Surface markers allowed visualization of the complex patterning of different cell types and the differential timing in their appearance. The phenotype of mesenchymal cells rapidly changed when they were grown as a monolayer, even without passage. This might explain the rapid loss of their potential to sustain tooth formation after re-association. Except for markers associated with vascularization, which is not maintained in vitro, the staining pattern in the mesenchyme of cultured re-associations was similar to that observed in situ. After implantation, vascularization and the cellular heterogeneity in the mesenchyme were similar to what was observed in developing molars. Besides tissue oxygenation and its role in mineralization of dental matrices, vascularization is involved in the progressive increase in mesenchymal cell heterogeneity, by allowing external cells to enter the mesenchyme.
Topics: Animals; Epithelium; Mesoderm; Mice; Odontogenesis; Tissue Engineering; Tooth
PubMed: 23319349
DOI: 10.1387/ijdb.120076hl -
Developmental Dynamics : An Official... May 2011Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null)...
Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null) Msx2(null/null) mutant is difficult to analyze, particularly along the anteroposterior axis, because of the complex effects of the double mutation on both ectoderm- and mesoderm-derived structures. Namely, in the mutant, formation of the apical ectodermal ridge (AER) is impaired anteriorly and, consequently, the subjacent mesenchyme does not form. Using the Cre/loxP system, we investigated the respective roles of Msx genes in ectoderm and mesoderm by generating conditional mutant embryos with no Msx activity solely in the mesoderm. In these mutants, the integrity of the ectoderm-derived AER was maintained, allowing formation of the anterior mesenchyme. With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity.
Topics: Animals; Cell Death; Cell Proliferation; Extremities; Homeodomain Proteins; In Situ Hybridization; Limb Buds; MSX1 Transcription Factor; Mesoderm; Mice; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 21465616
DOI: 10.1002/dvdy.22619 -
Current Topics in Developmental Biology 2015Reciprocal interactions between epithelial and mesenchymal tissues play a fundamental role in the morphogenesis of teeth and regulate all aspects of tooth development.... (Review)
Review
Reciprocal interactions between epithelial and mesenchymal tissues play a fundamental role in the morphogenesis of teeth and regulate all aspects of tooth development. Extensive studies on mouse tooth development over the past 25 years have uncovered the molecular details of the signaling networks mediating these interactions (reviewed by Jussila & Thesleff, 2012; Lan, Jia, & Jiang, 2014). Five conserved signaling pathways, namely, the Wnt, BMP, FGF, Shh, and Eda, are involved in the mediation of the successive reciprocal epithelial-mesenchymal cross talk which follows the general principle of morphogenetic interactions (Davidson, 1993). The pathways regulate the expression of transcription factors which confer the identity of dental epithelium and mesenchyme. The signals and transcription factors are integrated in complex signaling networks whose fine-tuning allows the generation of the variation in tooth morphologies. In this review, we describe the principles and molecular mechanisms of the epithelial-mesenchymal interactions regulating successive stages of tooth formation: (i) the initiation of tooth development, with special reference to the shift of tooth-forming potential from epithelium to mesenchyme; (ii) the morphogenesis of the tooth crown, focusing on the roles of epithelial signaling centers; (iii) the differentiation of odontoblasts and ameloblasts, which produce dentin and enamel, respectively; and (iv) the maintenance of dental stem cells, which support the continuous growth of teeth.
Topics: Animals; Epithelium; Gene Expression Regulation, Developmental; Humans; Mesoderm; Neural Crest; Odontogenesis; Signal Transduction; Stem Cells; Tooth
PubMed: 26589925
DOI: 10.1016/bs.ctdb.2015.07.006