156 research outputs found

    Tissue Origins and Interactions in the Mammalian Skull Vault

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    AbstractDuring mammalian evolution, expansion of the cerebral hemispheres was accompanied by expansion of the frontal and parietal bones of the skull vault and deployment of the coronal (fronto-parietal) and sagittal (parietal–parietal) sutures as major growth centres. Using a transgenic mouse with a permanent neural crest cell lineage marker, Wnt1-Cre/R26R, we show that both sutures are formed at a neural crest–mesoderm interface: the frontal bones are neural crest-derived and the parietal bones mesodermal, with a tongue of neural crest between the two parietal bones. By detailed analysis of neural crest migration pathways using X-gal staining, and mesodermal tracing by DiI labelling, we show that the neural crest–mesodermal tissue juxtaposition that later forms the coronal suture is established at E9.5 as the caudal boundary of the frontonasal mesenchyme. As the cerebral hemispheres expand, they extend caudally, passing beneath the neural crest–mesodermal interface within the dermis, carrying with them a layer of neural crest cells that forms their meningeal covering. Exposure of embryos to retinoic acid at E10.0 reduces this meningeal neural crest and inhibits parietal ossification, suggesting that intramembranous ossification of this mesodermal bone requires interaction with neural crest-derived meninges, whereas ossification of the neural crest-derived frontal bone is autonomous. These observations provide new perspectives on skull evolution and on human genetic abnormalities of skull growth and ossification

    Lineage-specific Gene Expression in the Sea Urchin Embryo

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    Within a few days of fertilization, the sea urchin embryo develops into a small differentiated organism consisting of about 1800 cells and capable of feeding, swimming, and the further ontogenic transformations required in the succeeding weeks of larval growth. A number of distinct cell lineages that are clearly specialized at the morphological and functional levels can be discerned in the advanced embryo, and many of these can be traced back to particular sets of early blastomeres. Classical cell lineage and experimental studies (Hörstadius 1939; for review, see Angerer and Davidson 1984) have shown that certain of these lineages appear to be specified, at least in part, in consequence of the maternal components inherited in those regions of egg cytoplasm occupied by their progenitor cells. Specification of others among the early cell lineages clearly depends on inductive interactions that occur between blastomeres during cleavage. For the molecular biologist, as for his predecessors, this rapidly developing and simply constructed embryo offers the advantages of experimental accessibility. Thus, in respect to direct molecular-level analyses of gene activity in the embryo, for both specific genes and overall transcript populations and their protein products, the sea urchin is at present the best known embryonic system (e.g., reviews of Hentschel and Birnstiel 1981; Davidson et al. 1982; Angerer and Davidson 1984)

    Oxidation behaviour of SiC/SiC ceramic matrix composites in air

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    Oxidation of silicon melt infiltrated SiC/SiC ceramic matrix composites (CMC) was studied in air at 1200–1400 °C for 1, 5, 24 and 48 h. Weight gain and oxide layer thickness measurements revealed the oxidation follows parabolic reaction kinetics with increase in temperature and time. XRD showed the extent of oxide layer (SiO2) formation was greatest after 48 h at 1400 °C: an observation confirmed by X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) analyses. Oxide layer thickness varied from 1 μm after 48 h at 1200 °C to 8 μm after 48 h at 1400 °C. Oxidation of SiC/SiC composites is both temperature and time dependent with an activation energy of 619 kJ mol−1. BN coatings around SiC fibres showed good resistance to oxidation even after 48 h at 1400 °C

    Lineage-specific Gene Expression in the Sea Urchin Embryo

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    Within a few days of fertilization, the sea urchin embryo develops into a small differentiated organism consisting of about 1800 cells and capable of feeding, swimming, and the further ontogenic transformations required in the succeeding weeks of larval growth. A number of distinct cell lineages that are clearly specialized at the morphological and functional levels can be discerned in the advanced embryo, and many of these can be traced back to particular sets of early blastomeres. Classical cell lineage and experimental studies (Hörstadius 1939; for review, see Angerer and Davidson 1984) have shown that certain of these lineages appear to be specified, at least in part, in consequence of the maternal components inherited in those regions of egg cytoplasm occupied by their progenitor cells. Specification of others among the early cell lineages clearly depends on inductive interactions that occur between blastomeres during cleavage. For the molecular biologist, as for his predecessors, this rapidly developing and simply constructed embryo offers the advantages of experimental accessibility. Thus, in respect to direct molecular-level analyses of gene activity in the embryo, for both specific genes and overall transcript populations and their protein products, the sea urchin is at present the best known embryonic system (e.g., reviews of Hentschel and Birnstiel 1981; Davidson et al. 1982; Angerer and Davidson 1984)

    Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons

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    During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unknown. Here we demonstrate in mouse embryos that the endothelin family member Edn3 (ref. 1), acting through the endothelin receptor EdnrA (refs 2, 3), directs extension of axons of a subset of sympathetic neurons from the superior cervical ganglion to a preferred intermediate target, the external carotid artery, which serves as the gateway to select targets, including the salivary glands. These findings establish a previously unknown mechanism of axonal pathfinding involving vascular-derived endothelins, and have broad implications for endothelins as general mediators of axonal growth and guidance in the developing nervous system. Moreover, they suggest a model in which newborn sympathetic neurons distinguish and choose between distinct vascular trajectories to innervate their appropriate end organs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62906/1/nature06859.pd

    Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes

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    Retinoids, vitamin A derivatives, are important regulators of the growth and differentiation of skin cells. Although retinoids are therapeutically used for several skin ailments, little is known about their effects on P2 receptors, known to be involved in various functions in the skin. DNA array analysis showed that treatment of normal human epidermal keratinocytes (NHEKs) with all-trans-retinoic acid (ATRA), an agonist to RAR (retinoic acid receptor), enhanced the expression of mRNA for the P2Y2 receptor, a metabotropic P2 receptor that is known to be involved in the proliferation of the epidermis. The expression of other P2 receptors in NHEKs was not affected by ATRA. ATRA increased the mRNA for the P2Y2 receptor in a concentration-dependent fashion (1 nM to 1 μM). Am80, a synthesized agonist to RAR, showed a similar enhancement, whereas 9-cis-retinoic acid (9-cisRA), an agonist to RXR (retinoid X receptor), enhanced P2Y2 gene expression to a lesser extent. Ca2+ imaging analysis showed that ATRA also increased the function of P2Y2 receptors in NHEKs. Retinoids are known to enhance the turnover of the epidermis by increasing both proliferation and terminal differentiation. The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs. Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs. This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling

    Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium

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    <p>Abstract</p> <p>Background</p> <p><it>Msx1 </it>and <it>Msx2</it>, which belong to the highly conserved <it>Nk </it>family of homeobox genes, display overlapping expression patterns and redundant functions in multiple tissues and organs during vertebrate development. <it>Msx1 </it>and <it>Msx2 </it>have well-documented roles in mediating epithelial-mesenchymal interactions during organogenesis. Given that both <it>Msx1 </it>and <it>Msx2 </it>are crucial downstream effectors of Bmp signaling, we investigated whether <it>Msx1 </it>and <it>Msx2 </it>are required for the Bmp-induced endothelial-mesenchymal transformation (EMT) during atrioventricular (AV) valve formation.</p> <p>Results</p> <p>While both <it>Msx1-/- </it>and <it>Msx2-/- </it>single homozygous mutant mice exhibited normal valve formation, we observed hypoplastic AV cushions and malformed AV valves in <it>Msx1-/-; Msx2-/- </it>mutants, indicating redundant functions of <it>Msx1 </it>and <it>Msx2 </it>during AV valve morphogenesis. In <it>Msx1/2 </it>null mutant AV cushions, we found decreased Bmp2/4 and <it>Notch1 </it>signaling as well as reduced expression of <it>Has2</it>, <it>NFATc1 </it>and <it>Notch1</it>, demonstrating impaired endocardial activation and EMT. Moreover, perturbed expression of chamber-specific genes <it>Anf</it>, <it>Tbx2</it>, <it>Hand1 </it>and <it>Hand2 </it>reveals mispatterning of the <it>Msx1/2 </it>double mutant myocardium and suggests functions of <it>Msx1 </it>and <it>Msx2 </it>in regulating myocardial signals required for remodelling AV valves and maintaining an undifferentiated state of the AV myocardium.</p> <p>Conclusion</p> <p>Our findings demonstrate redundant roles of <it>Msx1 </it>and <it>Msx2 </it>in regulating signals required for development of the AV myocardium and formation of the AV valves.</p
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