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BMC Developmental Biology Oct 2017Vertebrate head development depends on a series of interactions between many cell populations of distinct embryological origins. Cranial mesenchymal tissues have a dual...
BACKGROUND
Vertebrate head development depends on a series of interactions between many cell populations of distinct embryological origins. Cranial mesenchymal tissues have a dual embryonic source: - the neural crest (NC), which generates most of craniofacial skeleton, dermis, pericytes, fat cells, and tenocytes; and - the mesoderm, which yields muscles, blood vessel endothelia and some posterior cranial bones. The molecular players that orchestrate co-development of cephalic NC and mesodermal cells to properly construct the head of vertebrates remain poorly understood. In this regard, Six1 gene, a vertebrate homolog of Drosophila Sine Oculis, is known to be required for development of ear, nose, tongue and cranial skeleton. However, the embryonic origin and fate of Six1-expressing cells have remained unclear. In this work, we addressed these issues in the avian embryo model by using quail-chick chimeras, cephalic NC cultures and immunostaining for SIX1.
RESULTS
Our data show that, at early NC migration stages, SIX1 is expressed by mesodermal cells but excluded from the NC cells (NCC). Then, SIX1 becomes widely expressed in NCC that colonize the pre-otic mesenchyme. In contrast, in the branchial arches (BAs), SIX1 is present only in mesodermal cells that give rise to jaw muscles. At later developmental stages, the distribution of SIX1-expressing cells in mesoderm-derived tissues is consistent with a possible role of this factor in the myogenic program of all types of head muscles, including pharyngeal, extraocular and tongue muscles. In NC derivatives, SIX1 is notably expressed in perichondrium and chondrocytes of the nasal septum and in the sclera, although other facial cartilages such as Meckel's were negative at the stages considered. Moreover, in cephalic NC cultures, chondrocytes and myofibroblasts, not the neural and melanocytic cells express SIX1.
CONCLUSION
The present results point to a dynamic tissue-specific expression of SIX1 in a variety of cephalic NC- and mesoderm-derived cell types and tissues, opening the way for further analysis of Six1 function in the coordinated development of these two cellular populations during vertebrate head formation.
Topics: Animals; Embryo, Nonmammalian; Mesoderm; Neural Crest; Quail
PubMed: 29017464
DOI: 10.1186/s12861-017-0155-z -
Stem Cell Research & Therapy Aug 2010Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of... (Review)
Review
Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of cells in the developing organism to become the ancestors of skeletal muscle. Signals that control progression through the myogenic lineage converge on a battery of hierarchically organized transcription factors which modulate the cells to either remain in a primitive state or allow their commitment and differentiation into skeletal muscle fibers. A small population of cells will retain a largely unspecified state throughout development. Such stem cells, in conjunction with more committed myogenic progenitors, form a heterogeneous population that colonizes adult skeletal muscle as satellite cells. The satellite cell pool is responsible for the remarkable regenerative capacity of skeletal muscle. Similar to their counterparts during embryonic development, satellite cells are capable of self-renewal and can give rise to myogenic progeny. Impaired satellite cell homeostasis has been associated with numerous muscular disorders. Due to intense research efforts in the past two decades, the complex biology of muscle stem cells has now revealed some of its secrets and new avenues for the development of therapeutic molecules have emerged. In the present review we focus on the extrinsic mechanisms that control self-renewal, specification and differentiation of satellite cells and their significance for the development of biologic drugs.
Topics: Cell Differentiation; Humans; Intercellular Signaling Peptides and Proteins; Mesoderm; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Signal Transduction; Stem Cell Niche
PubMed: 20804582
DOI: 10.1186/scrt27 -
Scientific Data Dec 2016Mesoderm is the developmental precursor to myriad human tissues including bone, heart, and skeletal muscle. Unravelling the molecular events through which these lineages...
Mesoderm is the developmental precursor to myriad human tissues including bone, heart, and skeletal muscle. Unravelling the molecular events through which these lineages become diversified from one another is integral to developmental biology and understanding changes in cellular fate. To this end, we developed an in vitro system to differentiate human pluripotent stem cells through primitive streak intermediates into paraxial mesoderm and its derivatives (somites, sclerotome, dermomyotome) and separately, into lateral mesoderm and its derivatives (cardiac mesoderm). Whole-population and single-cell analyses of these purified populations of human mesoderm lineages through RNA-seq, ATAC-seq, and high-throughput surface marker screens illustrated how transcriptional changes co-occur with changes in open chromatin and surface marker landscapes throughout human mesoderm development. This molecular atlas will facilitate study of human mesoderm development (which cannot be interrogated in vivo due to restrictions on human embryo studies) and provides a broad resource for the study of gene regulation in development at the single-cell level, knowledge that might one day be exploited for regenerative medicine.
Topics: Biomarkers; Cell Differentiation; Chromatin; Humans; Mesoderm; Pluripotent Stem Cells; Transcription, Genetic
PubMed: 27996962
DOI: 10.1038/sdata.2016.109 -
Cellular and Molecular Life Sciences :... Mar 2021It is critical to specify a signal that directly drives the transition that occurs between cell states. However, such inferences are often confounded by indirect...
It is critical to specify a signal that directly drives the transition that occurs between cell states. However, such inferences are often confounded by indirect intercellular communications or secondary transcriptomic changes due to primary transcription factors. Although FGF is known for its importance during mesoderm-to-endothelium differentiation, its specific role and signaling mechanisms are still unclear due to the confounding factors referenced above. Here, we attempted to minimize the secondary artifacts by manipulating FGF and its downstream mediators with a short incubation time before sampling and protein-synthesis blockage in a low-density angioblastic/endothelial differentiation system. In less than 8 h, FGF started the conversion of KDR/PDGFRA nascent mesoderm into KDR/PDGFRA angioblasts, and the priming by FGF was necessary to endow endothelial formation 72 h later. Further, the angioblastic conversion was mediated by the FGFR1/BRAF/MEK/ERK pathway in mesodermal cells. Finally, two transcription factors, ETV2 and LMO2, were the early direct functional responders downstream of the FGF pathway, and ETV2 alone was enough to complement the absence of FGF. FGF's selective role in mediating the first-step, angioblastic conversion from mesoderm-to-endothelium thus allows for refined control over acquiring and manipulating angioblasts. The noise-minimized differentiation/analysis platform presented here is well-suited for studies on the signaling switches of other mesodermal-lineage fates as well.
Topics: Adaptor Proteins, Signal Transducing; Blood Vessels; Cell Differentiation; Cell Line; Fibroblast Growth Factors; Humans; LIM Domain Proteins; MAP Kinase Signaling System; Mesoderm; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Receptor, Fibroblast Growth Factor, Type 1; Transcription Factors; Vascular Endothelial Growth Factor A
PubMed: 32910224
DOI: 10.1007/s00018-020-03630-8 -
Scientific Reports Sep 2021The mesoderm is considered the youngest of the three germ layers. Although its morphogenesis has been studied in some metazoans, the molecular components underlying this...
The mesoderm is considered the youngest of the three germ layers. Although its morphogenesis has been studied in some metazoans, the molecular components underlying this process remain obscure for numerous phyla including the highly diverse Mollusca. Here, expression of Hairy and enhancer of split (HES), Mox, and myosin heavy chain (MHC) was investigated in Acanthochitona fascicularis, a representative of Polyplacophora with putative ancestral molluscan features. While AfaMHC is expressed throughout myogenesis, AfaMox1 is only expressed during early stages of mesodermal band formation and in the ventrolateral muscle, an autapomorphy of the polyplacophoran trochophore. Comparing our findings to previously published data across Metazoa reveals Mox expression in the mesoderm in numerous bilaterians including gastropods, polychaetes, and brachiopods. It is also involved in myogenesis in molluscs, annelids, tunicates, and craniates, suggesting a dual role of Mox in mesoderm and muscle formation in the last common bilaterian ancestor. AfaHESC2 is expressed in the ectoderm of the polyplacophoran gastrula and later in the mesodermal bands and in putative neural tissue, whereas AfaHESC7 is expressed in the trochoblasts of the gastrula and during foregut formation. This confirms the high developmental variability of HES gene expression and demonstrates that Mox and HES genes are pleiotropic.
Topics: Animals; Annelida; Biological Evolution; Gastrulation; Gene Expression Regulation, Developmental; Genetic Pleiotropy; Homeodomain Proteins; Mesoderm; Morphogenesis; Myosin Heavy Chains; Phylogeny; Polyplacophora; Transcription Factor HES-1; Urochordata
PubMed: 34504115
DOI: 10.1038/s41598-021-96711-y -
Genesis (New York, N.Y. : 2000) Jan 2009Interactions between adjacent epithelial and mesenchymal tissues represent a highly conserved mechanism in embryonic organogenesis. In particular, the ability of the... (Review)
Review
Interactions between adjacent epithelial and mesenchymal tissues represent a highly conserved mechanism in embryonic organogenesis. In particular, the ability of the mesenchyme to instruct cellular differentiation of the epithelium is a fundamental requirement for the morphogenesis of tubular structures such as those found in the kidneys, lungs, and the developing male reproductive system. Once the tubular structure has formed, it receives signals from the mesenchyme, which can control proliferation, patterning, and differentiation of the epithelium inside the tube. However, the epithelium is not a "silent partner" in this process, and epithelium-derived factors are often required for proper maintenance of the mesenchymal compartment. Although much emphasis has been placed on the characterization of mesenchymally-derived signals required for epithelial differentiation, it is important to note that epithelial-mesenchymal interactions are a two-way street wherein each compartment requires the presence of the other for proper tubule morphogenesis and function. In this review, we discuss epithelial-mesenchymal interactions in the processes of Wolffian duct and fetal testis cord development using the mouse as a model organism and propose inhibin beta A as a conserved mesenchyme-derived regulator in these two male-specific tubular structures.
Topics: Animals; Cell Communication; Cell Differentiation; Epithelium; Male; Mesoderm; Testis; Wolffian Ducts
PubMed: 18979542
DOI: 10.1002/dvg.20453 -
The International Journal of... 2006The cellular and developmental analysis of evolutionary-conserved genes directing bilaterian mesodermal and myogenic cell fate previously identified the hydromedusan... (Comparative Study)
Comparative Study Review
The cellular and developmental analysis of evolutionary-conserved genes directing bilaterian mesodermal and myogenic cell fate previously identified the hydromedusan entocodon and its differentiation product, the striated muscle, as mesodermal derivatives. In view of these findings we presented a hypothesis disputing the diploblast classification of cnidarians without providing further explanations for the apparent diploblasty of the polyp stage and the formation of the subepidermal striated muscle in those Medusozoa lacking the entocodon nodule (Seipel and Schmid, 2005). Hence we carried out a systematic review of the histological and experimental evidence for mesodermal differentiations in cnidarians. In anthozoan and scyphozoan but not in hydrozoan polyps the presumptive mesodermal elements include amoeboid cells, the mesentery retractor muscles and scleroblasts, all of which are embedded or deeply rooted in the extracellular matrix (mesoglea) and derive from the ectoblastemal cells invading the extracellular matrix from the gastrulation site during or shortly after endoderm formation. These data lend further support to the cnidarian mesodermate hypothesis, whereby cnidarians and bilaterians share a common triploblast ancestor, the Urtriploblast, a small, motile, possibly medusa-like organism that did not feature a sessile polyp stage in its life cycle. As a consequence the diploblasty of the hydrozoan polyps may represent a derived morphology resulting from heterochronic modulations of the gastrulation process after endoderm formation.
Topics: Animals; Cell Differentiation; Cnidaria; Germ Layers; Life Cycle Stages; Mesoderm; Models, Biological; Muscle, Skeletal
PubMed: 16892172
DOI: 10.1387/ijdb.062150ks -
Developmental Cell May 2017Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is...
Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Mesoderm; Spinal Cord; Vertebrates; Wnt Signaling Pathway
PubMed: 28457792
DOI: 10.1016/j.devcel.2017.04.002 -
Developmental Biology Jul 2012Paraxial mesoderm is the tissue which gives rise to the skeletal muscles and vertebral column of the body. A gene regulatory network operating in the formation of...
Paraxial mesoderm is the tissue which gives rise to the skeletal muscles and vertebral column of the body. A gene regulatory network operating in the formation of paraxial mesoderm has been described. This network hinges on three key factors, Wnt3a, Msgn1 and Tbx6, each of which is critical for paraxial mesoderm formation, since absence of any one of these factors results in complete absence of posterior somites. In this study we determined and compared the spatial and temporal patterns of expression of Wnt3a, Msgn1 and Tbx6 at a time when paraxial mesoderm is being formed. Then, we performed a comparative characterization of mutants in Wnt3a, Msgn1 and Tbx6. To determine the epistatic relationship between these three genes, and begin to decipher the complex interplay between them, we analyzed double mutant embryos and compared their phenotypes to the single mutants. Through the analysis of molecular markers in mutants, our data support the bipotential nature of the progenitor cells for paraxial mesoderm and establish regulatory relationships between genes involved in the choice between neural and mesoderm fates.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Developmental; Mesoderm; Mice; Mutation; Somites
PubMed: 22546692
DOI: 10.1016/j.ydbio.2012.04.012 -
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