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International Journal of Molecular... Aug 2021To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual... (Review)
Review
To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a population of bipotent neuromesodermal progenitors resident in the posterior region of the embryo generate both neural and mesodermal lineages. At later stages, the somitic mesoderm regulates aspects of neural patterning and differentiation of both central and peripheral neural progenitors. Reciprocally, neural precursors influence the paraxial mesoderm to regulate somite-derived myogenesis and additional processes by distinct mechanisms. Central to this crosstalk is the activity of the axial notochord, which, via sonic hedgehog signaling, plays pivotal roles in neural, skeletal muscle and cartilage ontogeny. Here, we discuss the cellular and molecular basis underlying this complex developmental plan, with a focus on the logic of sonic hedgehog activities in the coordination of the neural-mesodermal axis.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Mesoderm; Neural Tube
PubMed: 34502050
DOI: 10.3390/ijms22179141 -
Developmental Biology May 2020Vertebrate head morphogenesis involves carefully-orchestrated tissue growth and cell movements of the mesoderm and neural crest to form the distinct craniofacial...
Vertebrate head morphogenesis involves carefully-orchestrated tissue growth and cell movements of the mesoderm and neural crest to form the distinct craniofacial pattern. To better understand structural birth defects, it is important that we characterize the dynamics of these processes and learn how they rely on each other. Here we examine this question during chick head morphogenesis using time-lapse imaging, computational modeling, and experiments. We find that head mesodermal cells in culture move in random directions as individuals and move faster in the presence of neural crest cells. In vivo, mesodermal cells migrate in a directed manner and maintain neighbor relationships; neural crest cells travel through the mesoderm at a faster speed. The mesoderm grows with a non-uniform spatio-temporal profile determined by BrdU labeling during the period of faster and more-directed neural crest collective migration through this domain. We use computer simulations to probe the robustness of neural crest stream formation by varying the spatio-temporal growth profile of the mesoderm. We follow this with experimental manipulations that either stop mesoderm growth or prevent neural crest migration and observe changes in the non-manipulated cell population, implying a dynamic feedback between tissue growth and neural crest cell signaling to confer robustness to the system. Overall, we present a novel descriptive analysis of mesoderm and neural crest cell dynamics that reveals the coordination and co-dependence of these two cell populations during head morphogenesis.
Topics: Animals; Cell Division; Cell Movement; Cells, Cultured; Chick Embryo; Chickens; Computer Simulation; Coturnix; Ectoderm; Head; Mesoderm; Models, Biological; Morphogenesis; Neural Crest; Neural Tube; Time-Lapse Imaging
PubMed: 32084354
DOI: 10.1016/j.ydbio.2020.02.010 -
Developmental Biology Sep 2017The physical basis of morphogenesis is a fascinating concern that has been a longstanding interest of developmental biologists. In this review, I attempt to incorporate... (Review)
Review
The physical basis of morphogenesis is a fascinating concern that has been a longstanding interest of developmental biologists. In this review, I attempt to incorporate earlier and recent biophysical concepts and data to explain basic features of early limb bud morphogenesis. In particular, I discuss the influence of mesenchymal cohesion and physical properties that might contribute to phase separation of the bud from the lateral plate, the possibility that the early dorsoventral limb bud axis is moulded by the surface ectoderm, and endogenous electric fields that might contribute to oriented cell movements which generate the early limb bud. A combination of quantitative biophysical experimentation and modelling will likely advance this field.
Topics: Animals; Biophysical Phenomena; Cell Movement; Cell Polarity; Electricity; Limb Buds; Mesoderm; Morphogenesis
PubMed: 28669818
DOI: 10.1016/j.ydbio.2017.06.034 -
International Journal of Molecular... Apr 2019Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding of how mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activity contributes to the regulation of ureteric bud branching morphogenesis, which dictates the final size, shape, and nephron number of the kidney. Recent studies also demonstrate that the MAPK/ERK pathway is directly involved in nephrogenesis, regulating both the maintenance and differentiation of the nephrogenic mesenchyme. Interestingly, aberrant MAPK/ERK signaling is linked to many cancers, and recent studies suggest it also plays a role in the most common pediatric renal cancer, Wilms' tumor.
Topics: Animals; Cell Differentiation; Humans; Kidney; MAP Kinase Signaling System; Mesoderm; Organogenesis
PubMed: 30974877
DOI: 10.3390/ijms20071779 -
Developmental Dynamics : An Official... Mar 2016Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly... (Review)
Review
Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.
Topics: Animals; Embryo, Mammalian; Epithelium; Humans; Mesoderm; Organogenesis; Signal Transduction; Viscera
PubMed: 26638186
DOI: 10.1002/dvdy.24373 -
TheScientificWorldJournal Nov 2010We review a recently discovered developmental mechanism. Anterior-posterior positional information for the vertebrate trunk is generated by sequential interactions... (Review)
Review
We review a recently discovered developmental mechanism. Anterior-posterior positional information for the vertebrate trunk is generated by sequential interactions between a timer in the early nonorganizer mesoderm (NOM) and the Spemann organizer (SO). The timer is characterized by temporally collinear activation of a series of Hox genes in the early ventral and lateral mesoderm (i.e., the NOM) of the Xenopus gastrula. This early Hox gene expression is transient, unless it is stabilized by signals from the SO. The NOM and the SO undergo timed interactions due to morphogenetic movements during gastrulation, which lead to the formation of an anterior-posterior axial pattern and stable Hox gene expression. When separated from each other, neither the NOM nor the SO is able to induce anterior-posterior pattern formation of the trunk. We present a model describing that the NOM acquires transiently stable hox codes and spatial collinearity, and that morphogenetic movements then continually bring new cells from the NOM within the range of SO signals that cause transfer of the mesodermal pattern to a stable pattern in neurectoderm and, thereby, create patterned axial structures. In doing so, the age of the NOM, but not the age of the SO, defines positional values along the anterior-posterior axis. We postulate that the temporal information from the NOM is linked to mesodermal Hox expression. The role of the SO for trunk patterning turns out to be the induction of neural tissue as prerequisite for neural hox patterning. Apparently, development of a stable anterior-posterior pattern requires neural hox patterning. We believe that this mechanism represents a developmental principle.
Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mesoderm; Morphogenesis; Neural Plate; Organizers, Embryonic; Vertebrates; Xenopus
PubMed: 21057733
DOI: 10.1100/tsw.2010.208 -
Cellular and Molecular Life Sciences :... Oct 2018Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell... (Review)
Review
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβCD271EMCNDLK1CD73 primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.
Topics: Autoimmune Diseases; Cell Lineage; Embryonic Development; Endothelial Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesoderm; Pluripotent Stem Cells; Spheroids, Cellular
PubMed: 29992471
DOI: 10.1007/s00018-018-2871-3 -
Nature Aug 2020Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic...
Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic mesoderm, which control posterior elongation, exhibit a high level of aerobic glycolysis that is reminiscent of the metabolic status of cancer cells experiencing the Warburg effect. Glycolytic activity downstream of fibroblast growth factor controls WNT signalling in the tail bud. In the neuromesodermal precursors of the tail bud, WNT signalling promotes the mesodermal fate that is required for sustained axial elongation, at the expense of the neural fate. How glycolysis regulates WNT signalling in the tail bud is currently unknown. Here we used chicken embryos and human tail bud-like cells differentiated in vitro from induced pluripotent stem cells to show that these cells exhibit an inverted pH gradient, with the extracellular pH lower than the intracellular pH, as observed in cancer cells. Our data suggest that glycolysis increases extrusion of lactate coupled to protons via the monocarboxylate symporters. This contributes to elevating the intracellular pH in these cells, which creates a favourable chemical environment for non-enzymatic β-catenin acetylation downstream of WNT signalling. As acetylated β-catenin promotes mesodermal rather than neural fate, this ultimately leads to activation of mesodermal transcriptional WNT targets and specification of the paraxial mesoderm in tail bud precursors. Our work supports the notion that some tumour cells reactivate a developmental metabolic programme.
Topics: Acetylation; Amnion; Animals; Body Patterning; Chick Embryo; Glycolysis; Humans; Hydrogen-Ion Concentration; Lactic Acid; Mesoderm; Wnt Proteins; beta Catenin
PubMed: 32581357
DOI: 10.1038/s41586-020-2428-0 -
The International Journal of... 2009In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in... (Review)
Review
In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in the paraxial mesoderm along the anterior-posterior axis are responsible for the development of a skeleton with the appropriate vertebral formula, i.e. a specific number of cervical, thoracic, lumbar, sacral and caudal vertebrae. These control mechanisms are complex and involve molecules of different kinds, including transcription factors, like those encoded by the Hox genes, and signalling molecules, like those involved in Gdf11, FGF, retinoic acid or WNT signalling. Recent experiments indicate that most of the positional information for the paraxial mesoderm is encoded during the initial steps of its development in the presomitic mesoderm, although it is only decoded later during differentiation of the somites. The genesis of positional identity may be linked to the process of somitogenesis, which also occurs in the presomitic mesoderm as a result of complex interactions involving oscillatory activity of components of the Notch and WNT signalling pathways and antagonistic gradients of FGF/WNT and retinoic acid. The possible connections between Hox genes and all these signalling processes to generate a properly patterned axial skeleton are discussed in this review.
Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mesoderm; Signal Transduction; Somites; Spine; Vertebrates
PubMed: 19247958
DOI: 10.1387/ijdb.072276mm -
ELife Mar 2016Experiments in mice shed new light on an elusive population of embryonic cells called neuromesodermal progenitors.
Experiments in mice shed new light on an elusive population of embryonic cells called neuromesodermal progenitors.
Topics: Animals; Gene Expression Regulation, Developmental; Mesoderm; Mice
PubMed: 26949247
DOI: 10.7554/eLife.14830