21 research outputs found
Dental Epithelial Stem Cells Express the Developmental Regulator Meis1
MEIS1 is a key developmental regulator of several organs and participates in stem cell maintenance in different niches. However, despite the murine continuously growing incisor being a well described model for the study of adult stem cells, Meis1 has not been investigated in a dental context. Here, we uncover that Meis1 expression in the tooth is confined to the epithelial compartment. Its expression arises during morphogenesis and becomes restricted to the mouse incisor epithelial stem cell niche, the labial cervical loop. Meis1 is specifically expressed by Sox2(+) stem cells, which give rise to all dental epithelial cell lineages. Also, we have found that Meis1 in the incisor is coexpressed with potential binding partner Pbx1 during both embryonic and adult stages. Interestingly, Meis2 is present in different areas of the forming tooth and it is not expressed by dental epithelial stem cells, suggesting different roles for these two largely homologous genes. Additionally, we have established the expression patterns of Meis1 and Meis2 during tongue, hair, salivary gland and palate formation. Finally, analysis of Meis1-null allele mice indicated that, similarly, to SOX2, MEIS1 is not essential for tooth initiation, but might have a role during adult incisor renewal.Peer reviewe
Lunatic Fringe, FGF, and BMP Regulate the Notch Pathway during Epithelial Morphogenesis of Teeth
AbstractTeeth develop as epithelial appendages, and their morphogenesis is regulated by epithelialâmesenchymal interactions and conserved signaling pathways common to many developmental processes. A key event during tooth morphogenesis is the transition from bud to cap stage when the epithelial bud is divided into specific compartments distinguished by morphology as well as gene expression patterns. The enamel knot, a signaling center, forms and regulates the shape and size of the tooth. Mesenchymal signals are necessary for epithelial patterning and for the formation and maintenance of the epithelial compartments. We studied the expression of Notch pathway molecules during the bud-to-cap stage transition of the developing mouse tooth. Lunatic fringe expression was restricted to the epithelium, where it formed a boundary flanking the enamel knot. The Lunatic fringe expression domains overlapped only partly with the expression of Notch1 and Notch2, which were coexpressed with Hes1. We examined the regulation of Lunatic fringe and Hes1 in cultured explants of dental epithelium. The expression of Lunatic fringe and Hes1 depended on mesenchymal signals and both were positively regulated by FGF-10. BMP-4 antagonized the stimulatory effect of FGF-10 on Lunatic fringe expression but had a synergistic effect with FGF-10 on Hes1 expression. Recombinant Lunatic fringe protein induced Hes1 expression in the dental epithelium, suggesting that Lunatic fringe can act also extracellularly. Lunatic fringe mutant mice did not reveal tooth abnormalities, and no changes were observed in the expression patterns of other Fringe genes. We conclude that Lunatic fringe may play a role in boundary formation of the enamel knot and that Notch-signaling in the dental epithelium is regulated by mesenchymal FGFs and BMP
Potilas- ja asiakasturvallisuudelle uusi kansallinen mittaristo
Uudessa mittaristossa on jokaisen sote-ammattilaisen arkea koskettavia osia
Potilas- ja asiakasturvallisuudelle uusi kansallinen mittaristo
Uudessa mittaristossa on jokaisen sote-ammattilaisen arkea koskettavia osia.</p
Regulation of Calvarial Osteogenesis by Concomitant De-repression of GLI3 and Activation of IHH Targets
Loss-of-function mutations in GLI3 and IHH cause craniosynostois and reduced osteogeneiss, respectively. In this study, we show that ihh ligand, the receptor Ptch1 and Gli transcription factors are differentialyy expressed in embryonic mouse calvaria osteogenic condenstions. We show that in both ihh(-/-) and Gli3(Xt-J/Xt-J) embroyonic mice, the normal gene expression architecture is lost and this results in disorganized calvarial bone developement. RUNX2 is a master regulatory transciption factor controlling osteogenesis. In the absence of Gli3, RUNX2 isoform II and IHH are upregulated, and RUNX2 isoform I downregulated. This is consistent with the expandeed and aberant osteogenesis observed in Gli3Xt-J/Xt-J mice, and consistent RunX2-t expression by relatively immature osteoprogenitors. ihh-/- mice exhibited small calvarial bones HH target genes, Ptch1 and Gli1, were absent. This indicates that IHH is the functional HH ligand, and that it is not compensated by another HH ligand. To decipher the roles and potential interaction of Gli3 and ihh. we generated ihh-/-; gli3Xt-J/Xt-J compound mutant mice. Even in the absence of ihh, Gli3 deletion was sufficient to induce aberrant precocious ossification across the developing suture, indicating that the carniosyostosis pehnotype of Gli3Xt-J/Xt-J mice is not dependent on IHH ligand. Also we found that ihh was not required for Runx2 expression as the expression of RUNX2 target genes was unaffected by deletion of Ihh. To test whether RUNX2 has a role upstream of IHH we performed RUNX2 siRNA knock down experiements in WT calvarial osteoblasts and explants and found that Ihh expression is suppressed. Our results show that IHH is the functional HH ligand in the embroynic mouse calvaria osteogenic condensations, where it regulates the progression of osteoblastic differentation. As GLI3 represses the expression of Runx2-II abd Ihh, and also elevats the Runx2-I expression, and as IHH may be regulated by RUNX2 these results raise the possibility of a regualtory feedback circuit to control calvarial osteogenesis and suture patency. Taken together RUNX2-controlled osteoblastic cell fate is regulated by IHH through concomitant inhibition of GLI3-repressor formation and activation of downstreams targets.Peer reviewe
Potilas- ja asiakasturvallisuuden tilannekuva ja seurantamenettelyt : Ehdotus seurannan mittaristoksi
Suomessa ei ole saatavilla kansallista potilas- ja asiakasturvallisuuden tilannekuvaa. Turvallisuutta koskevia tietoja leimaa hajanaisuus ja pirstaleisuus. Tietoja kerÀtÀÀn ja tilannetta seurataan epÀyhtenÀisesti paikallisella, mahdollisesti alueellisella sekÀ kapeasta nÀkökulmasta myös kansallisella tasolla. TÀmÀn seurauksena potilas- ja asiakasturvallisuuden kattava arviointi ei ole mahdollista. Myös potilas- ja asiakasturvallisuuden ohjaus ja valvonta on vaikeutunut.
VN TEAS -hankkeessa on koottu mittaristo, joka mahdollistaa sote-organisaatioiden vertailun ja vertaiskehittÀmisen. Mittaristo jakautuu kolmeen osa-alueeseen: 1) rakenteita ja kÀytÀnteitÀ tukevat tarkistuslistaindikaattorit, 2) kuuma linja -indikaattorit, jotka kuvaavat vakavien haittoja ja niiden ilmoittamis- ja kÀsittelykÀytÀntöjÀ tavoitteena nopeuttaa ja tehostaa haittojen kÀsittelyÀ ja ennaltaehkÀisyÀ toimintayksiköissÀ; sekÀ 3) keskeiset mÀÀrÀlliset vertailuindikaattorit, joista kansallinen vertailu on mahdollista aloittaa. Alueilla ja toimintayksikkötasolla mittaristoa olisi mahdollista hyödyntÀÀ vapaaehtoisuuteen perustuvalla vertaiskehittÀmisen mallilla.
Mittareiden valinta on tehty laajasta valikoimasta, joista valtaosa on toimintayksiköissÀ kÀytössÀ. Valinta on perustunut sekÀ hankkeessa työskennelleiden ettÀ ulkopuolisten asiantuntijoiden laajaan konsensukseen, kansainvÀlisiin esimerkkeihin ja suosituTÀmÀ julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa (tietokayttoon.fi). Julkaisun sisÀllöstÀ vastaavat tiedon tuottajat, eikÀ tekstisisÀltö vÀlttÀmÀttÀ edusta valtioneuvoston nÀkemystÀ
Hiki, Àhky ja loikka - Osallistujien pedagogisia mietteitÀ ja ideoita hankkeen varrelta
DIGIJOUJOU-hankkeessa tyoÌskennelleet opettajat ovat hankkeen toimintavuosien 2017-2019 aikana pohtineet opetuksen ja oppimisen digitaalisuutta ja joustavuutta eri naÌkoÌkulmista: mitaÌ digitaalisuus ja joustavuus suomen ja ruotsin opiskelussa tarkoittaa, miten soveltaa, lisaÌtaÌ ja kehittaÌaÌ digitaalisuutta ja joustavuutta omassa opetuksessa ja opiskelijoiden oppimisessa. Hankelaisten blogikirjoituksissa naÌemme askeleita opettajien omasta ja yhdessaÌ muiden kanssa oppimisesta hankkeen edetessaÌ; epaÌvarmuus muuttuu varmuudeksi, ajoittainen digiaÌhky oman asiantuntijuuden kasvuksi ja joustavuus osaksi opettajan arkipedagogiikkaa. Antoisia ja inspiroivia lukuhetkiaÌ!
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