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Biomaterials Jul 2018Tissue engineering therapies using adult stem cells derived from neural crest have sought accessible tissue sources of these cells because of their potential...
Tissue engineering therapies using adult stem cells derived from neural crest have sought accessible tissue sources of these cells because of their potential pluripotency. In this study, the gingiva and oral mucosa and their associated stem cells were investigated. Biopsies of these tissues produce neither scarring nor functional problems and are relatively painless, and fresh tissue can be obtained readily during different chairside dental procedures. However, the embryonic origin of these cells needs to be clarified, as does their evolution from the perinatal period to adulthood. In this study, the embryonic origin of gingival fibroblasts were determined, including gingival stem cells. To do this, transgenic mouse models were used to track neural crest derivatives as well as cells derived from paraxial mesoderm, spanning from embryogenesis to adulthood. These cells were compared with ones derived from abdominal dermis and facial dermis. Our results showed that gingival fibroblasts are derived from neural crest, and that paraxial mesoderm is involved in the vasculogenesis of oral tissues during development. Our in vitro studies revealed that the neuroectodermal origin of gingival fibroblasts (or gingival stem cells) endows them with multipotential properties as well as a specific migratory and contractile phenotype which may participate to the scar-free properties of the oral mucosa. Together, these results illustrate the high regenerative potential of neural crest-derived stem cells of the oral mucosa, including the gingiva, and strongly support their use in cell therapy to regenerate tissues with impaired healing.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell- and Tissue-Based Therapy; Fibroblasts; Gingiva; Humans; Mesoderm; Mice; Models, Animal; Morphogenesis; Mouth Mucosa; Neural Crest; Neural Stem Cells; Regeneration; Transplants; Wound Healing
PubMed: 29715594
DOI: 10.1016/j.biomaterials.2018.04.036 -
Development (Cambridge, England) Jul 2003At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are...
At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are required for the inducing activity of the epidermis in chick and amphibian embryos. Here, we analyze the molecular mechanisms of neural crest induction by the mesoderm in Xenopus embryos. Using a recombination assay, we show that prospective paraxial mesoderm induces a panel of neural crest markers (Slug, FoxD3, Zic5 and Sox9), whereas the future axial mesoderm only induces a subset of these genes. This induction is blocked by a dominant negative (dn) form of FGFR1. However, neither dnFGFR4a nor inhibition of Wnt signaling prevents neural crest induction in this system. Among the FGFs, FGF8 is strongly expressed by the paraxial mesoderm. FGF8 is sufficient to induce the neural crest markers FoxD3, Sox9 and Zic5 transiently in the animal cap assay. In vivo, FGF8 injections also expand the Slug expression domain. This suggests that FGF8 can initiate neural crest formation and cooperates with other DLMZ-derived factors to maintain and complete neural crest induction. In contrast to Wnts, eFGF or bFGF, FGF8 elicits neural crest induction in the absence of mesoderm induction and without a requirement for BMP antagonists. In vivo, it is difficult to dissociate the roles of FGF and WNT factors in mesoderm induction and neural patterning. We show that, in most cases, effects on neural crest formation were parallel to altered mesoderm or neural development. However, neural and neural crest patterning can be dissociated experimentally using different dominant-negative manipulations: while Nfz8 blocks both posterior neural plate formation and neural crest formation, dnFGFR4a blocks neural patterning without blocking neural crest formation. These results suggest that different signal transduction mechanisms may be used in neural crest induction, and anteroposterior neural patterning.
Topics: Animals; Body Patterning; Ectoderm; Fibroblast Growth Factor 8; Fibroblast Growth Factors; Genes, Dominant; In Situ Hybridization; Mesoderm; Neural Crest; Neurons; Protein Structure, Tertiary; RNA; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 4; Receptors, Fibroblast Growth Factor; Recombination, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Xenopus laevis
PubMed: 12783784
DOI: 10.1242/dev.00531 -
Anatomy and Embryology Dec 2006It is currently thought that the mechanism underlying somitogenesis is linked to a molecular oscillator, the segmentation clock, and to gradients of signaling molecules... (Review)
Review
It is currently thought that the mechanism underlying somitogenesis is linked to a molecular oscillator, the segmentation clock, and to gradients of signaling molecules within the paraxial mesoderm. Here, we review the current picture of this segmentation clock and gradients, and use this knowledge to critically ask: What is the basis for periodicity and directionality of somitogenesis?
Topics: Animals; Biological Clocks; Body Patterning; Embryonic Development; Signal Transduction; Somites; Wnt Proteins
PubMed: 17024300
DOI: 10.1007/s00429-006-0124-y -
Seminars in Cell & Developmental Biology Jul 2022A critical stage in the development of all vertebrate embryos is the generation of the body plan and its subsequent patterning and regionalisation along the main... (Review)
Review
A critical stage in the development of all vertebrate embryos is the generation of the body plan and its subsequent patterning and regionalisation along the main anterior-posterior axis. This includes the formation of the vertebral axial skeleton. Its organisation begins during early embryonic development with the periodic formation of paired blocks of mesoderm tissue called somites. Here, we review axial patterning of somites, with a focus on studies using amniote model systems - avian and mouse. We summarise the molecular and cellular mechanisms that generate paraxial mesoderm and review how the different anatomical regions of the vertebral column acquire their specific identity and thus shape the body plan. We also discuss the generation of organoids and embryo-like structures from embryonic stem cells, which provide insights regarding axis formation and promise to be useful for disease modelling.
Topics: Animals; Body Patterning; Embryonic Development; Gene Expression Regulation, Developmental; Mesoderm; Mice; Somites; Spine; Vertebrates
PubMed: 34690064
DOI: 10.1016/j.semcdb.2021.10.003 -
Current Topics in Developmental Biology 2018The skeletal muscle lineage derives from the embryonic paraxial mesoderm (PM) which also gives rise to the axial skeleton, the dermis of the back, brown fat, meninges,... (Review)
Review
The skeletal muscle lineage derives from the embryonic paraxial mesoderm (PM) which also gives rise to the axial skeleton, the dermis of the back, brown fat, meninges, and endothelial cells. Direct conversion was pioneered in skeletal muscle with overexpression of the transcription factor MyoD which can convert fibroblasts to a muscle fate. In contrast, directed differentiation of skeletal muscle from pluripotent cells (PC) in vitro has proven to be very difficult compared to other lineages and has only been achieved recently. Experimental strategies recapitulating myogenesis in vitro from mouse and human PC (ES/iPS) have now been reported and all rely on early activation of Wnt signaling at the epiblast stage. This leads to induction of neuromesodermal progenitors that can subsequently be induced to a PM fate and to skeletal muscle. These protocols can efficiently produce fetal muscle fibers and immature satellite cells. These new in vitro systems now open the possibility to better understand human myogenesis and to develop in vitro disease models as well as cell therapy approaches.
Topics: Animals; Bone Morphogenetic Proteins; Cell Differentiation; Humans; Mesoderm; Models, Biological; Muscle Development; Stem Cells
PubMed: 29801528
DOI: 10.1016/bs.ctdb.2018.03.003 -
Advances in Experimental Medicine and... 2006The formation of the neural crest has been traditionally considered a classic example of secondary induction, where signals form one tissue elicit a response in a... (Review)
Review
The formation of the neural crest has been traditionally considered a classic example of secondary induction, where signals form one tissue elicit a response in a competent responding tissue. Interactions of the neural plate with paraxial mesoderm or nonneural ectoderm can generate neural crest. Several signaling pathways converge at the border between neural and nonneural ectoderm where the neural crest will form. Among the molecules identified in this process are members of the BMP, Wnt, FGF and Notch signaling pathways. The concerted action of these signals and their downstream targets will define the identity of the neural crest.
Topics: Animals; Body Patterning; Bone Morphogenetic Proteins; Developmental Biology; Ectoderm; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Humans; Mesoderm; Neural Crest; Receptors, Notch; Signal Transduction; Wnt Proteins
PubMed: 17076273
DOI: 10.1007/978-0-387-46954-6_2 -
Anatomy and Embryology May 1995We report on the formation and early differentiation of the somites in the avian embryo. The somites are derived from the avian embryo. The somites are derived from the... (Review)
Review
We report on the formation and early differentiation of the somites in the avian embryo. The somites are derived from the avian embryo. The somites are derived from the mesoderm which, in the body (excluding the head), is subdivided into four compartments: the axial, paraxial, intermediate and lateral plate mesoderm. Somites develop from the paraxial mesoderm and constitute the segmental pattern of the body. They are formed in pairs by epithelialization, first at the cranial end of the paraxial mesoderm, proceeding caudally, while new mesenchyme cells enter the paraxial mesoderm as a consequence of gastrulation. After their formation, which depends upon cell-cell and cell-matrix interactions, the somites impose segmental pattern upon peripheral nerves and vascular primordia. The newly formed somite consists of an epithelial ball of columnar cells enveloping mesenchymal cells within a central cavity, the somitocoel. Each somite is surrounded by extracellular matrix material connecting the somite with adjacent structures. The competence to form skeletal muscle is a unique property of the somites and becomes realized during compartmentalization, under control of signals emanating from surrounding tissues. Compartmentalization is accompanied by altered patterns of expression of Pax genes within the somite. These are believed to be involved in the specification of somite cell lineages. Somites are also regionally specified, giving rise to particular skeletal structures at different axial levels. This axial specification appears to be reflected in Hox gene expression. MyoD is first expressed in the dorsomedial quadrant of the still epithelial somite whose cells are not yet definitely committed. During early maturation, the ventral wall of the somite undergoes an epithelio-mesenchymal transition forming the sclerotome. The sclerotome later becomes subdivided into rostral and caudal halves which are separated laterally by von Ebner's fissure. The lateral part of the caudal half of the sclerotome mainly forms the ribs, neural arches and pedicles of vertebrae, whereas within the lateral part of the rostral half the spinal nerve develops. The medially migrating sclerotomal cells form the peri-notochordal sheath, and later give rise to the vertebral bodies and intervertebral discs. The somitocoel cells also contribute to the sclerotome. The dorsal half of the somite remains epithelial and is referred to as the dermomyotome because it gives rise to the dermis of the back and the skeletal musculature. the cells located within the lateral half of the dermomyotome are the precursors of the muscles of the hypaxial domain of the body, whereas those in the medial half are precursors of the epaxial (back) muscles.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Cell Differentiation; Chick Embryo; Gene Expression Regulation, Developmental; Mesoderm; Muscle, Skeletal; Spine
PubMed: 7625610
DOI: 10.1007/BF00304424 -
The FEBS Journal Apr 2016During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites.... (Review)
Review
During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites. Somites are sequentially formed at the anterior end of the presomitic mesoderm (PSM) resulting from functional interactions between the oscillatory activity of signals promoting segmentation and a moving wavefront of tissue competence to those signals, eventually generating a constant flow of new somites at regular intervals. According to the current model for somitogenesis, the wavefront results from the combined activity of two opposing functional gradients in the PSM involving the Fgf, Wnt and retinoic acid (RA) signaling pathways. Here, I use published data to evaluate the wavefront model. A critical analysis of those studies seems to support a role for Wnt signaling, but raise doubts regarding the extent to which Fgf and RA signaling contribute to this process.
Topics: Animals; Humans; Mesoderm; Morphogenesis; Signal Transduction; Somites
PubMed: 26662366
DOI: 10.1111/febs.13622 -
Development (Cambridge, England) Aug 1995The spatial distribution of the cranial paraxial mesoderm and the neural crest cells during craniofacial morphogenesis of the mouse embryo was studied by...
The spatial distribution of the cranial paraxial mesoderm and the neural crest cells during craniofacial morphogenesis of the mouse embryo was studied by micromanipulative cell grafting and cell labelling. Results of this study show that the paraxial mesoderm and neural crest cells arising at the same segmental position share common destinations. Mesodermal cells from somitomeres I, III, IV and VI were distributed to the same craniofacial tissues as neural crest cells of the forebrain, the caudal midbrain, and the rostral, middle and caudal hindbrains found respectively next to these mesodermal segments. This finding suggests that a basic meristic pattern is established globally in the neural plate ectoderm and paraxial mesoderm during early mouse development. Cells from these two sources mixed extensively in the peri-ocular, facial, periotic and cervical mesenchyme. However, within the branchial arches a distinct segregation of these two cell populations was discovered. Neural crest cells colonised the periphery of the branchial arches and enveloped the somitomere-derived core tissues on the rostral, lateral and caudal sides of the arch. Such segregation of cell populations in the first three branchial arches is apparent at least until the 10.5-day hindlimb bud stage and could be important for the patterning of the skeletal and myogenic derivatives of the arches.
Topics: Animals; Brain; Branchial Region; Cell Movement; Cell Survival; Culture Techniques; Dimethylformamide; Embryo, Mammalian; Face; Fluorescent Antibody Technique; Mesoderm; Mice; Mice, Transgenic; Morphogenesis; Neural Crest; Skull
PubMed: 7671820
DOI: 10.1242/dev.121.8.2569 -
Developmental Biology Oct 1998In the avian embryo, epithelialization of the segmental plate and formation of an epithelial dermomyotome depend on signals from the neural tube and the ectoderm...
In the avian embryo, epithelialization of the segmental plate and formation of an epithelial dermomyotome depend on signals from the neural tube and the ectoderm overlying the paraxial mesoderm. In this study, we report that ectoderm removal in combination with barrier insertion between the axial organs and the segmental plate leads to an induction of BMP-4 expression in the paraxial mesoderm. In the lateral plate, ectoderm removal alone leads to an increase of BMP-4 expression. Application of BMP-4 protein results in a lack of epithelialization of the paraxial mesoderm. In order to investigate whether the loss of epithelial structures after these manipulations can be attributed to a change in cell fate, a change in cell proliferation, or the induction of apoptosis, the paraxial mesoderm was tested for expression of Msx-2, BMP-2, BMP-4, and BMP-7. Moreover, BrdU and TUNEL staining were carried out. The inhibition of epithelialization after ectoderm removal alone and after segregation of the axial organs is accompanied neither by an increase in apoptosis nor by a reduction of the proliferation rate in the paraxial mesoderm. On the other hand, an ectopic BMP-4 expression in the paraxial mesoderm after ectoderm removal in combination with barrier insertion coincides with the occurrence of apoptotic cells and reduction of proliferation rate in this tissue. Increase of apoptosis and decrease in cell proliferation are observed in the paraxial and lateral plate mesoderm also after application of BMP-4 protein.
Topics: Animals; Apoptosis; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Cell Division; Chick Embryo; Ectoderm; Epithelium; Gene Expression Regulation, Developmental; In Situ Hybridization; Mesoderm
PubMed: 9769177
DOI: 10.1006/dbio.1998.9011