1. |
- El Shahawy, Maha, et al.
(författare)
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Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid
- 2017
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Ingår i: Plos Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.
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2. |
- El Shahawy, Maha, et al.
(författare)
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Sonic Hedgehog Signaling Is Required for Cyp26 Expression during Embryonic Development
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:9
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Tidskriftsartikel (refereegranskat)abstract
- Deciphering how signaling pathways interact during development is necessary for understanding the etiopathogenesis of congenital malformations and disease. In several embryonic structures, components of the Hedgehog and retinoic acid pathways, two potent players in development and disease are expressed and operate in the same or adjacent tissues and cells. Yet whether and, if so, how these pathways interact during organogenesis is, to a large extent, unclear. Using genetic and experimental approaches in the mouse, we show that during development of ontogenetically different organs, including the tail, genital tubercle, and secondary palate, Sonic hedgehog (SHH) loss-of-function causes anomalies phenocopying those induced by enhanced retinoic acid signaling and that SHH is required to prevent supraphysiological activation of retinoic signaling through maintenance and reinforcement of expression of the Cyp26 genes. Furthermore, in other tissues and organs, disruptions of the Hedgehog or the retinoic acid pathways during development generate similar phenotypes. These findings reveal that rigidly calibrated Hedgehog and retinoic acid activities are required for normal organogenesis and tissue patterning.
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3. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Abnormal hair development and apparent follicular transformation to mammary gland in the absence of Hedgehog signaling
- 2007
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Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807. ; 12:1, s. 99-112
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Tidskriftsartikel (refereegranskat)abstract
- Here, we show that removing the Shh receptor Smoothened from the skin epithelium results in a seemingly contradictory constellation of phenotypes including cellular disorganization, altered proliferation, and loss of hair follicle (HF) progenitors. We provide evidence that the lack of Smoothened in the epithelium results in excess Shh levels in the mesenchyme. Thus, the observed defects can be attributed not only to decreased epithelial Shh signaling, but increased mesenchymal Shh signalling. The latter contributes to exuberant HF induction, while the former depletes the resulting follicular stem cell niches. Two additional, unanticipated epithelial requirements for Shh relate to the robust acquisition of appropriate cell type identities: In the mutant mice, follicular outer root sheath takes on an epidermal character, and certain HF disappear altogether, having adopted a strikingly mammary gland-like fate. Our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.
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4. |
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5. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Expression patterns of the Tmem16 gene family during cephalic development in the mouse
- 2009
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Ingår i: Gene Expression Patterns. - : Elsevier BV. - 1567-133X. ; 9:3, s. 178-191
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Tidskriftsartikel (refereegranskat)abstract
- Tmem16a, Tmem16c, Tmem16f, Tmem16h and Tmem16k belong to the newly identified Tmem16 gene family encoding eight-pass transmembrane proteins. We have analyzed the expression patterns of these genes during mouse cephalic development. In the central nervous system, Tmem16a transcripts were abundant in the ventricular neuroepithelium, whereas the other Tmem16 family members were readily detectable in the subventricular zone and differentiating fields. In the rostral spinal cord, Tmem16f expression was highest in the motor neuron area. In the developing eye, the highest amounts of Tmem16a transcripts were detected in the lens epithelium, hyaloid plexus and outer layer of the retina, while the other family members were abundant in the retinal ganglionic cell layer. Interestingly, throughout development, Tmem16a expression in the inner ear was robust and restricted to a subset of cells within the epithelium, which at later stages formed the organ of Corti. The stria vascularis was particularly rich in Tmem16a and Tmem16f mRNA. Other sites of Tmem16 expression included cranial nerve and dorsal root ganglia, meningeal precursors and the pituitary. Tmem16c and Tmem16f transcripts were also patent in the submandibular autonomic ganglia. A conspicuous feature of Tmem16a was its expression along the walls of blood vessels as well as in cells surrounding the trigeminal and olfactory nerve axons. In organs developing through epithelial-mesenchymal interactions, such as the palate, tooth and tongue, the above five Tmem16 family members showed interesting dynamic expression patterns as development proceeded. Finally and remarkably, osteoblasts and chondrocytes were particularly loaded with Tmem16a, Tmem16c and Tmem16f transcripts.
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6. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Nuclear translocation of antizyme and expression of ornithine decarboxylase and antizyme are developmentally regulated
- 2001
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Ingår i: Developmental Dynamics. ; 220:3, s. 259-275
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Tidskriftsartikel (refereegranskat)abstract
- The polyamines are important regulators of cell growth and differentiation. Cells acquire polyamines by energy-dependent transport and by synthesis where the highly regulated ornithine decarboxylase (ODC) catalyzes the first and rate-controlling step. Inactivation of ODC is mainly exerted by antizyme (AZ), a 20--25 kDa polyamine-induced protein that binds to ODC, inactivates it, and targets it for degradation by the 26S proteasome without ubiquitination. In the present study, we have performed a systematic analysis of the expression of ODC and AZ, at the mRNA and protein levels, during mouse development. The expression patterns for ODC and AZ were found to be developmentally regulated, suggesting important functions for the polyamines in early embryogenesis, axonogenesis, epithelial-mesenchymal interaction, and in apoptosis. In addition, AZ protein was found to translocate to the nucleus in a developmentally regulated manner. The nuclear localization is consistent with the fact that the amino acid sequence of AZ exhibits features that characterize nuclear proteins. Interestingly, we found that cultivation of mandibular components of the first branchial arch in the presence of a selective proteasome inhibitor caused ODC accumulation in the nucleus of a subset of cells, suggesting that the observed nuclear translocation of AZ is linked to proteasome-mediated ODC degradation in the nucleus. The presence of AZ in the nucleus may suggest that nuclear ODC activity is under tight control, and that polyamine production can be rapidly interrupted when those developmental events, which depend on access to nuclear polyamines, have been completed.
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7. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization
- 2002
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Ingår i: Development. ; 129:23, s. 5323-5337
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Tidskriftsartikel (refereegranskat)abstract
- Sonic hedgehog (Shh), a member of the mammalian hedgehog (Hh) family, plays a key role during embryogenesis and organogenesis. Tooth development, odontogenesis, is governed by sequential and reciprocal epithelial-mesenchymal interactions. Genetic removal of Shh activity from the dental epithelium, the sole source of Shh during tooth development, alters tooth growth and cytological organization within both the dental epithelium and mesenchyme of the tooth. In this model it is not clear which aspects of the phenotype represent the direct action of Shh on a target tissue or indirect effects due to deficiencies in reciprocal signalings between the epithelial and mesenchymal components. To distinguish between these two alternatives and extend our understanding of Shh’s actions in odontogenesis, we have used the Cre-loxP system to remove Smoothened (Smo) activity in the dental epithelium. Smo, a seven-pass membrane protein is essential for the transduction of all Hh signals. Hence, removal of Smo activity from the dental epithelium should block Shh signaling within dental epithelial derivatives while preserving normal mesenchymal signaling. Here we show that Shh-dependent interactions occur within the dental epithelium itself. The dental mesenchyme develops normally up until birth. In contrast, dental epithelial derivatives show altered proliferation, growth, differentiation and polarization. Our approach uncovers roles for Shh in controlling epithelial cell size, organelle development and polarization. Further, we provide evidence that Shh signaling between ameloblasts and the overlying stratum intermedium may involve subcellular localization of Ptc2 and Gli1 mRNAs, both of which are targets of Shh signaling in these cells.
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8. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides
- 2001
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Ingår i: Developmental Biology. ; 236:2, s. 364-386
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Tidskriftsartikel (refereegranskat)abstract
- Sonic Hedgehog (Shh) and Indian Hedgehog (Ihh) are members of the Hedgehog (Hh) family of signaling molecules known to be involved in embryonic patterning and morphogenesis. The Hh proteins undergo an autocatalytic cleavage to yield an N-terminal and a C-terminal peptide, with the signaling capacities confined to the N peptide. Drosophila Hh-N has been shown to act via both short- and long-range signaling. In vertebrates, however, attempts to directly demonstrate Shh (SHH) or Ihh (IHH) proteins at a distance from producing cells have been largely unsuccessful. Furthermore, the fact that the Hh N peptides occur in a cholesterol-modified, membrane-tethered form is not easily reconciled with long-range signaling. This study used optimized immunohistochemistry combined with tissue separation and biochemical analyses in vivo and in vitro to determine the range of action of SHH and IHH in the mouse embryo. In all embryonic structures studied, we detect signaling peptides in producing cells, but we also find that ligands move over considerable distances depending on the tissue. These data provide direct evidence for the presence of Hedgehog signaling peptides in target compartments, suggesting a direct long-range action without a need for secondary mediators. Visualization of Hedgehog proteins in target tissues was achieved only under conditions that allowed proteoglycan/glycosaminoglycan (PG/GAG) preservation. Furthermore, we show that induced changes of the composition of PG/GAG in the tooth alter SHH signaling. These data suggest a crucial role for PG/GAGs in Hedgehog movement.
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9. |
- Larsson, Birgitta, et al.
(författare)
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Extracts of ECL-cell granules/vesicles and of isolated ECL cells from rat oxyntic mucosa evoke a Ca2+ second messenger response in osteoblastic cells
- 2001
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Ingår i: Regulatory Peptides. ; 97:2-3, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Surgical removal of the acid-producing part of the stomach (oxyntic mucosa) reduces bone mass through mechanisms not yet fully understood. The existence of an osteotropic hormone produced by the so-called ECL cells has been suggested. These cells, which are numerous in the oxyntic mucosa, operate under the control of circulating gastrin. Both gastrin and an extract of the oxyntic mucosa decrease blood calcium and stimulate Ca2+ uptake into bone. Conceivably, gastrin lowers blood calcium indirectly by releasing a hypothetical hormone from the ECL cells. The present study investigated, by means of fura-2 fluorometry, the effect of extracts of preparations enriched in ECL cell granules/vesicles from rat oxyntic mucosa on mobilization of intracellular Ca2+ in three osteoblast-like cell lines, UMR-106.01, MC3T3-E1 and Saos-2, and of extracts of isolated ECL cells in UMR-106.01 cells. The extracts were found to induce a dose-related rapid increase in intracellular Ca2+ concentrations in the osteoblast-like cells. The response was not due to histamine or pancreastatin, known ECL cell constituents, and could be abolished by pre-digesting the extracts with exo-aminopeptidase. The results show that the increase in [Ca2+](i) reflects a mobilization of Ca2+ from the endoplasmic reticulum. The observation of an increase in [Ca2+](i) also in murine embryonic fibroblasts show that the response is not limited to osteoblastic cells. The finding that the extracts evoked a typical Ca2+ -mediated second messenger response in osteoblastic cells provides evidence for the existence of a novel osteotropic peptide hormone (gastrocalcin), produced in the ECL cells, and supports the view that gastrectomy-induced osteopathy may reflect a lack of this hormone.
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10. |
- Lundquist, Patrik, 1969, et al.
(författare)
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Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts.
- 2000
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Ingår i: Calcified Tissue International. - 0171-967X. ; 67:1, s. 60-7
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Tidskriftsartikel (refereegranskat)abstract
- In odontoblasts as well as osteoblasts, a number of mechanisms for the inflow and extrusion of Ca2+ have been demonstrated. The entrance of Ca2+ ions into odontoblasts occurs mainly through voltage-gated calcium channels. Extrusion of Ca2+ is found to be an ATP-dependent process and, in addition, Na+/Ca2+-antiports exist, which are provoked by extracellular Na+. The aim of this study was to identify the Na+/Ca2+-antiport isoforms expressed in dentinogenically active rat incisor odontoblasts and to make a comparison with different osteoblastic cells. Using RT-PCR and RNAse protection assay, we demonstrated the expression of three different isoforms, NaCa 3, 7, and 10, of the NCX1-encoded antiport in odontoblasts and osteoblastic cells. When incubated in the presence of Na+, dissected rat incisor odontoblasts as well as the osteoblastic cells extruded Ca2+ ions, as detected by chlorotetracycline and Fura-2 fluorometry, thus supporting a physiological role for the detected isoform expression. Odontoblasts and rat calvarial osteoblasts, as well as osteoblast-like cell lines UMR-106.01 and Saos-2, were shown to exhibit identical phenotypes of Na+/Ca2+-antiport isoform expression, different from the expression patterns of other tissues. The significance of this specific expression pattern is unknown, but there is a possibility that it is in some way related to the unique demands on these cell types to produce mineralized connective tissue.
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11. |
- Reibring, Claes-Göran, 1955, et al.
(författare)
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Distinct and Overlapping Expression Patterns of the Homer Family of Scaffolding Proteins and Their Encoding Genes in Developing Murine Cephalic Tissues.
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- In mammals Homer1, Homer2 and Homer3 constitute a family of scaffolding proteins with key roles in Ca2+ signaling and Ca2+ transport. In rodents, Homer proteins and mRNAs have been shown to be expressed in various postnatal tissues and to be enriched in brain. However, whether the Homers are expressed in developing tissues is hitherto largely unknown. In this work, we used immunohistochemistry and in situ hybridization to analyze the expression patterns of Homer1, Homer2 and Homer3 in developing cephalic structures. Our study revealed that the three Homer proteins and their encoding genes are expressed in a wide range of developing tissues and organs, including the brain, tooth, eye, cochlea, salivary glands, olfactory and respiratory mucosae, bone and taste buds. We show that although overall the three Homers exhibit overlapping distribution patterns, the proteins localize at distinct subcellular domains in several cell types, that in both undifferentiated and differentiated cells Homer proteins are concentrated in puncta and that the vascular endothelium is enriched with Homer3 mRNA and protein. Our findings suggest that Homer proteins may have differential and overlapping functions and are expected to be of value for future research aiming at deciphering the roles of Homer proteins during embryonic development.
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12. |
- Reibring, Claes-Göran, 1955, et al.
(författare)
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Expression Patterns and Subcellular Localization of Carbonic Anhydrases Are Developmentally Regulated during Tooth Formation.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Carbonic anhydrases (CAs) play fundamental roles in several physiological events, and emerging evidence points at their involvement in an array of disorders, including cancer. The expression of CAs in the different cells of teeth is unknown, let alone their expression patterns during odontogenesis. As a first step towards understanding the role of CAs during odontogenesis, we used immunohistochemistry, histochemistry and in situ hybridization to reveal hitherto unknown dynamic distribution patterns of eight CAs in mice. The most salient findings include expression of CAII/Car2 not only in maturation-stage ameloblasts (MA) but also in the papillary layer, dental papilla mesenchyme, odontoblasts and the epithelial rests of Malassez. We uncovered that the latter form lace-like networks around incisors; hitherto these have been known to occur only in molars. All CAs studied were produced by MA, however CAIV, CAIX and CARPXI proteins were distinctly enriched in the ruffled membrane of the ruffled MA but exhibited a homogeneous distribution in smooth-ended MA. While CAIV, CAVI/Car6, CAIX, CARPXI and CAXIV were produced by all odontoblasts, CAIII distribution displayed a striking asymmetry, in that it was virtually confined to odontoblasts in the root of molars and root analog of incisors. Remarkably, from initiation until near completion of odontogenesis and in several other tissues, CAXIII localized mainly in intracellular punctae/vesicles that we show to overlap with LAMP-1- and LAMP-2-positive vesicles, suggesting that CAXIII localizes within lysosomes. We showed that expression of CAs in developing teeth is not confined to cells involved in biomineralization, pointing at their participation in other biological events. Finally, we uncovered novel sites of CA expression, including the developing brain and eye, the olfactory epithelium, melanoblasts, tongue, notochord, nucleus pulposus and sebaceous glands. Our study provides important information for future single or multiple gene targeting strategies aiming at deciphering the function of CAs during odontogenesis.
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13. |
- Reibring, Claes-Göran, 1955, et al.
(författare)
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Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:11
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Tidskriftsartikel (refereegranskat)abstract
- BMP signaling is crucial for differentiation of secretory ameloblasts, the cells that secrete enamel matrix. However, whether BMP signaling is required for differentiation of maturation-stage ameloblasts (MA), which are instrumental for enamel maturation into hard tissue, is hitherto unknown. To address this, we used an in vivo genetic approach which revealed that combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA. These fail to exhibit a ruffled apical plasma membrane and to reabsorb enamel matrix proteins, leading to enamel defects mimicking hypomaturation amelogenesis imperfecta. Furthermore, subsets of mutant MA underwent pathological single or collective cell migration away from the ameloblast layer, forming cysts and/or exuberant tumor-like and gland-like structures. Massive apoptosis in the adjacent stratum intermedium and the abnormal cell-cell contacts and cell-matrix adhesion of MA may contribute to this aberrant behavior. The mutant MA also exhibited severely diminished tissue non-specific alkaline phosphatase activity, revealing that this enzyme's activity in MA crucially depends on BMP2 and BMP4 inputs. Our findings show that combined BMP2 and BMP4 signaling is crucial for survival of the stratum intermedium and for proper development and function of MA to ensure normal enamel maturation.
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14. |
- Vazirisani, Forugh, 1967, et al.
(författare)
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Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and nasal cavity of the mouse
- 2010
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Ingår i: European Journal of Oral Sciences. - 1600-0722. ; 118:3, s. 221-236
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyse the hitherto largely unknown expression patterns of some specific cellular and extracellular molecules during palate and nasal cavity development. We show that epithelia of the developing palate and the vomerine epithelium express similar sets of structural proteins. With the exception of keratin 15, which becomes barely detectable in the elevated palatal shelves, nearly all of these become upregulated at the presumptive areas of fusion and in the adhering epithelia of the palate and nasal septum. In vivo and in vitro analyses indicated that keratin 15 protein reduction is independent of Tgfβ-Alk5 signaling. Foxa1 expression also highlighted the regionalization of the palatal and nasal epithelia. Due to lack of reliable markers of the palatal periderm, the fate of peridermal cells has been controversial. We identified LewisX/SSEA1 as a specific peridermal marker, and showed that numerous peridermal cells remain trapped in the medial epithelial seam (MES). The fate of these cells is likely apoptosis together with the rest of MES cells, as we provided further strong evidence for this event. Heparan sulphate, chondroitin-6-sulphate and versican displayed dynamically changing distribution patterns. The hitherto unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting.
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15. |
- Vazirisani, Forugh, 1967, et al.
(författare)
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Fate-mapping of the epithelial seam during palatal fusion rules out epithelial-mesenchymal transformation.
- 2005
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606. ; 285:2, s. 490-495
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Tidskriftsartikel (refereegranskat)abstract
- During palatogenesis, fusion of the palatine shelves is a crucial event, the failure of which results in the birth defect, cleft palate. The fate of the midline epithelial seam (MES), which develops transiently upon contact of the two palatine shelves, is still strongly debated. Three major mechanisms underlying the regression of the MES upon palatal fusion have been proposed: (1) apoptosis has been evidenced by morphological and molecular criteria; (2) epithelial-mesenchymal transformation has been suggested based on ultrastructural and lipophilic dye cell labeling observations; and (3) migration of MES cells toward the oral and nasal areas has been proposed following lipophilic dye cell labeling. To verify whether epithelial-mesenchymal transformation of MES cells takes place during murine palatal fusion, we used the Cre/lox system to genetically mark Sonic hedgehog- and Keratin-14-expressing palatal epithelial cells and to identify their fate in vivo. Our analyses provide conclusive evidence that rules out the occurrence of epithelial-mesenchymal transformation of MES cells.
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16. |
- Zhao, Dawei, 1963, et al.
(författare)
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Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is developmentally regulated
- 2006
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Ingår i: European Journal of Oral Sciences. ; 114:6, s. 517-523
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Tidskriftsartikel (refereegranskat)abstract
- Different sodium-dependent inorganic phosphate (Pi) uptake mechanisms play a major role in cellular Pi homeostasis. The function and detailed distribution patterns of the type III Na+-phosphate cotransporter PiT-2 in different organs during development are still largely unknown. We therefore examined the temporospatial expression patterns of Pit2 during murine odontogenesis. Odontoblasts were always devoid of Pit2 expression, whereas only a transient but strong expression was detected in young secretory ameloblasts. However, the stratum intermedium and, later on, the papillary layer and cells of the subodontoblastic layer exhibited high amounts of Pit2 mRNA, which increased gradually as the tooth matured. Hormonal treatment or Pi starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2 also functions as a retroviral receptor, and functional membrane-localized protein was confirmed throughout the dental papilla/pulp by demonstrating cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a receptor. The distinct pattern of Pit2 expression during odontogenesis suggests that its Pi-transporter function may be important for homeostasis of dental cells and not specifically for mineralization of the dental extracellular matrices. The expression of viral receptors in enamel-forming cells and the dental pulp may be of pathological significance.
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17. |
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18. |
- Carlsson, Sven G., 1935, et al.
(författare)
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Reduction of dental fear: psychophysiological correlates.
- 1986
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Ingår i: Community dentistry and oral epidemiology. - 0301-5661. ; 14:5, s. 253-7
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Tidskriftsartikel (refereegranskat)abstract
- EMG, HR and SCR were continuously recorded during two Standardized Dental Examinations (SDE) of 15 dental phobics. Following the first SDE, the patients were assigned to two treatment groups, one receiving systematic desensitization followed by two separate amalgam restorations and one premedicated with Valium for the two restorations. The dentist rated the patients' behavior on a 5-point scale. Corah's Dental Anxiety Scale (DAS) was used prior to the first SDE and following the second SDE. The second SDE was conducted on a separate occasion following the second restoration. No significant correlations were found between any of the physiological measures and either the dentist's ratings or the second DAS or DAS change scores. Significant differences found between the two treatment groups on the dentist's ratings, second DAS, and change scores were not reflected by the physiological measures.
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19. |
- Carlsson, Sven G., 1935, et al.
(författare)
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Reduction of tension in fearful dental patients.
- 1980
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Ingår i: Journal of the American Dental Association (1939). - 0002-8177. ; 101:4, s. 638-41
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Tidskriftsartikel (refereegranskat)abstract
- A method based on the principles of desensitization, biofeedback, and control by patients is described; ten patients who had severe dental fear were given therapy before conventional treatment was begun.
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20. |
- Linde, Anders, 1944, et al.
(författare)
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Creation of new bone by an osteopromotive membrane technique: An experimental study in rats
- 1993
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Ingår i: J Oral Maxillofac Surg. ; 51, s. 892-897
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Tidskriftsartikel (refereegranskat)abstract
- Domes, 5 and 8 mm in diameter, were made of expanded polytetrafluorethylene membrane with different degrees of stiffness and internodal distance. The domes were placed on denuded calvarial bones of rats and covered by the skin and periosteal flaps. Histologic evaluation 9 to 16 weeks after surgery showed the formation of various amounts of new bone on the calvarial bone surface inside the domes. The amount of bone neogenesis was dependent on membrane qualities, such as stiffness and porosity, and the length of the healing period. In the most successful experiments, about 80% of the dome volume was filled with newly formed bone, whereas in other experiments considerable amounts of connective tissue were present. Using bioabsorbable membrane domes proved less successful in that they did not maintain their shape and thus did not provide space for bone formation. This study showed that it is possible to obtain bone neogenesis by an osteopromotive membrane technique. This possibility may eventually be of great significance for reconstructive surgery.
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21. |
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22. |
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23. |
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24. |
- Lundgren, Ted, 1959, et al.
(författare)
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Junctional proteins and Ca2+ transport in the rat odontoblast-like cell line MRPC-1.
- 2001
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Ingår i: Calcified tissue international. - 0171-967X. ; 68:3, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- A transcellular bulk flow of Ca2+ ions through the odontoblast layer is of central importance during dentinogenesis. For this, specialized mechanisms may exist, which by a concerted action, gate Ca2+ into the proximal end of the cells and extrude the ions towards the mineralization front. To elucidate these mechanisms, an in vitro model would be useful. Mature odontoblasts are, however, post-mitotic cells and cannot be propagated in cell culture. The aim of the present study was, therefore, to characterize the odontoblast-like rat cell line MRPC-1(1) with regard to transcellular Ca2+ transport, barrier function, and intercellular junctions when cultured on membranes in Transwell chambers. The MRPC-1 cells grew as epithelial-like cells in a continuous bilayer separated by a thin collagenous matrix and with intercellular junctional complexes. They exhibited properties of a low-resistance epithelium, maintained a Ca(2+)-dependent diffusion barrier, and exhibited a functional diversity between the two cell layers. MRPC-1 cells expressed ZO-1, occludin, E-, and N-cadherins in addition to alpha-, beta-, gamma- and p120cat catenins, thereby demonstrating some traits in common with, but also differences from, epithelial cells and major differences from fibroblasts. The transcellular Ca2+ flux was inhibitable by nifedipine unidirectionally, giving evidence for an active intracellular Ca2+ transport through voltage-gated channels of the L-type. Similarities with native odontoblasts indicate that MRPC-1 cells may be useful for in vitro studies of transcellular Ca2+ transport mechanisms of importance for the calcification process.
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25. |
- Lundgren, Ted, 1959, et al.
(författare)
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The use of the stable isotope 44Ca in studies of calcium incorporation into dentin.
- 1994
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Ingår i: Journal of microscopy. - 0022-2720. ; 173:Pt 2, s. 149-54
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation into rat incisor dentin of two calcium isotopes, the stable 44Ca and the radioactive 45Ca, was studied using secondary ion mass spectrometry (SIMS) step-scanning and imaging, and autoradiography, respectively. The results demonstrated a time-dependent incorporation of the calcium isotopes into the mineral phase of dentin. With the SIMS step-scanning, detecting 44Ca, the ion yield was high in the odontoblasts 2 min after intravenous injection. After 10 min a marked increase in signal intensity was found at the dentin mineralization front. This result was consistent with those obtained by 45Ca autoradiography; a peak of incorporation occurred 10 min after injection of the isotope. Likewise, localization of 44Ca to the mineralization front could be demonstrated 10 min after injection by SIMS imaging. In images obtained at earlier intervals, no such increase in ion yield could be detected. The results show that the nonradioactive, stable isotope 44Ca can be used as a marker for biomineralization in a similar way to radioactive 45Ca.
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26. |
- Lundquist, Patrik, 1969, et al.
(författare)
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Phosphate and calcium uptake by rat odontoblast-like MRPC-1 cells concomitant with mineralization.
- 2002
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 17:10, s. 1801-13
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that odontoblasts are instrumental in translocating Ca2+ and inorganic phosphate (Pi) ions during the mineralization of dentin. The aim of this study was to characterize cellular Pi and Ca2+ uptake in the novel rat odontoblast-like cell line mineralizing rat pulpal cell line (MRPC) 1 during mineralization to see if changes in the ion transport activity would occur as the cultures develop and begin forming a mineralized matrix. MRPC-1 cells were cultured in chemically defined medium containing ascorbate and Pi, and cultures were specifically analyzed for cellular P, and Ca2+ uptake activities and expression of type II high-capacity Na+-Pi cotransporters. The odontoblast-like phenotype of the cell line was ascertained by monitoring the expression of collagen type I and dentin phosphopoprotein (DPP). Mineralized nodule formation started at day 9 after confluency and then rapidly increased. Ca2+ uptake by the cells showed a maximum during the end of the proliferative phase (days 5-7). Pi uptake declined to a basal level during proliferation and then was up-regulated simultaneously with the onset of mineralization to a level fourfold of the basal uptake, suggesting an initiating and regulatory role for cellular Pi uptake in mineral formation. This up-regulation coincided with a conspicuously increased glycosylation of NaPi-2a, indicating an activation of this Na+-Pi cotransporter. The study showed that MRPC-1 cells express an odontoblast-like phenotype already at the onset of culture, but that to mineralize the collagenous extracellular matrix (ECM) that formed, a further differentiation involving their ion transporters is necessary.
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