Stem cell regulation plays a crucial role during development and homeostasis. Here, an essential source of Wnts from Gli1+ stem/progenitor cells was identified in the murine molar. Loss of Wnt production in Gli1+ apical stem/progenitor cells led to loss of Axin2 at the root apex, mis-regulation of SOX9, loss of BMP and Hh signaling, and truncation of root development. In the absence of Wnt signals, the root epithelium lost its integrity and epithelial identity. This phenotype could be partially mimicked by loss of Sox9 in the Gli1 population. Stabilization of Wnt signaling in the apical papilla led to rapid unordered differentiation of hard tissues and fragmentation of the epithelial root sheath. Wnt signaling from Gli1+ stem/progenitor cells, therefore, orchestrates root development, coordinating mesenchymal and epithelial interactions via SOX9 to regulate stem/progenitor cell expansion and differentiation. Our results demonstrate that disparate stem/progenitor cell populations are unified in their fundamental signaling interactions.
The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig's epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.
- MeSH
- abnormality zubů genetika MeSH
- dítě MeSH
- ektodysplasiny genetika MeSH
- fenotyp MeSH
- kavita zubní dřeně abnormality MeSH
- lidé MeSH
- mladiství MeSH
- moláry abnormality embryologie MeSH
- myši MeSH
- odontogeneze genetika MeSH
- rentgenová mikrotomografie MeSH
- signální transdukce MeSH
- zubní kořen abnormality embryologie MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, and pathogenesis of teeth and bones have been intensely studied, there is currently no tool to accurately follow the dynamics of growth and healing of these vital tissues in space and time. Here, we present the BEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) approach, which allows precise quantification of development, regeneration, remodeling, and healing in any type of calcified tissue across different species. Using mouse teeth as model the turnover rate of continuously growing incisors was quantified, and role of hard/soft diet on molar root growth was shown. Furthermore, the dynamics of bones and teeth growth in lizards, frogs, birds, and zebrafish was uncovered. This approach represents an effective, highly reproducible, and versatile tool that opens up diverse possibilities in developmental biology, bone and tooth healing, tissue engineering, and disease modeling.
- MeSH
- dánio pruhované * MeSH
- kosti a kostní tkáň MeSH
- myši MeSH
- vývoj kostí MeSH
- zubní kořen MeSH
- zuby * fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Nobelova cena 2008, LAV, HTLV III, SPID,
- MeSH
- AIDS etiologie prevence a kontrola přenos MeSH
- HIV infekce etiologie prevence a kontrola přenos MeSH
- HIV MeSH
- klinické laboratorní techniky dějiny metody trendy MeSH
- lidé MeSH
- nemoci opic přenos MeSH
- Sida MeSH
- zoonózy přenos MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
V článku je popisovaná 30letá historie onemocnění AIDS od diagnostiky prvních klinických případů v r. 1981, po objev nového virového agens (v r. 1983), které onemocnění vyvolává. Jsou uváděny spory o prioritu objevu viru HIV a přiznání prvenství francouzskému týmu z Pasteurova institutu v Paříži i konečné potvrzení tohoto názoru vyjádřené udělením Nobelovy ceny v r. 2008 Luc Montagnierovi a jeho spolupracovnici Francoise Barré-Sinoussi.
The 30-year natural history of AIDS disease is presented from the first clinical cases reported in 1981 to the identification of the HIV as the etiological agent of the disease. The priority dispute between Robert C. Gallo and Luc Montagnier over the discovery of the human immunodeficiency virus is briefly addressed. The final confirmation of the French priority was provided by the fact that the Nobel Prize in Medicine 2008 was awarded to Luc Montagnier and Francoise Barré- -Sinoussi from the Pasteur Institute in Paris.
- Klíčová slova
- SPID, HTLV III, LAV, Nobelova cena 2008,
- MeSH
- AIDS dějiny epidemiologie etiologie MeSH
- dějiny 20. století MeSH
- HIV-1 imunologie izolace a purifikace patogenita MeSH
- HIV-2 imunologie izolace a purifikace patogenita MeSH
- HIV imunologie izolace a purifikace patogenita MeSH
- homosexualita mužská MeSH
- infekce přenášené vektorem klasifikace MeSH
- klinický obraz nemoci MeSH
- lidé MeSH
- nemoci primátů epidemiologie přenos virologie MeSH
- Nobelova cena MeSH
- Sida MeSH
- výročí a významné události MeSH
- významné osobnosti MeSH
- Check Tag
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- historické články MeSH
- Geografické názvy
- Afrika MeSH
- Francie MeSH
- Haiti MeSH
- Spojené státy americké MeSH