Members of the fibroblast growth factor (FGF) family have myriad functions during development of both non-vertebrate and vertebrate organisms. One of these family members, FGF10, is largely expressed in mesenchymal tissues and is essential for postnatal life because of its critical role in development of the craniofacial complex, as well as in lung branching. Here, we review the function of FGF10 in morphogenesis of craniofacial organs. Genetic mouse models have demonstrated that the dysregulation or absence of FGF10 function affects the process of palate closure, and FGF10 is also required for development of salivary and lacrimal glands, the inner ear, eye lids, tongue taste papillae, teeth, and skull bones. Importantly, mutations within the FGF10 locus have been described in connection with craniofacial malformations in humans. A detailed understanding of craniofacial defects caused by dysregulation of FGF10 and the precise mechanisms that underlie them offers new opportunities for development of medical treatments for patients with birth defects and for regenerative approaches for cancer patients with damaged gland tissues.

• Klíčová slova
• FGF10, craniofacial development, eyelid, inner ear, lacrimal gland, palate, salivary gland, taste papillae,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The patterning of repeated structures is a major theme in developmental biology, and the inter-relationship between spacing and size of such structures is an unresolved issue. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a crucial regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development; however, this effect does not occur at the level of gene transcription. Rather, our experimental data, together with computational modeling, indicate that FGF10 modulates the range of Wnt effects, likely via induction of Sostdc1 expression. We suggest that modification of the reach of Wnt signaling could be due to local changes in morphogen diffusion, representing a novel mechanism in this tissue context, and we propose that this phenomenon might be involved in a broader array of mammalian developmental processes.

• Klíčová slova
• FGF, Taste papilla, Tongue, Wnt,
• MeSH
• adaptorové proteiny signální transdukční MeSH
• biologické modely MeSH
• chuťové pohárky embryologie   metabolismus   MeSH
• fibroblastový růstový faktor 10 nedostatek   genetika   metabolismus   MeSH
• intracelulární signální peptidy a proteiny nedostatek   genetika   metabolismus   MeSH
• kostní morfogenetické proteiny genetika   metabolismus   MeSH
• membránové proteiny nedostatek   genetika   metabolismus   MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• počítačová simulace MeSH
• protein-serin-threoninkinasy MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• rozvržení tělního plánu genetika   fyziologie   MeSH
• signální dráha Wnt * MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• Fgf10 protein, mouse MeSH Prohlížeč
• fibroblastový růstový faktor 10 MeSH
• intracelulární signální peptidy a proteiny MeSH
• kostní morfogenetické proteiny MeSH
• membránové proteiny MeSH
• protein-serin-threoninkinasy MeSH
• proteiny hedgehog MeSH
• Shh protein, mouse MeSH Prohlížeč
• Sostdc1 protein, mouse MeSH Prohlížeč
• Spry2 protein, mouse MeSH Prohlížeč

The fibroblast growth factors (FGFs) constitute one of the largest growth factor families, and several ligands and receptors in this family are known to play critical roles during tongue development. In order to provide a comprehensive foundation for research into the role of FGFs during the process of tongue formation, we measured the transcript levels by quantitative PCR and mapped the expression patterns by in situ hybridization of all 22 Fgfs during mouse tongue development between embryonic days (E) 11.5 and E14.5. During this period, Fgf5, Fgf6, Fgf7, Fgf9, Fgf10, Fgf13, Fgf15, Fgf16 and Fgf18 could all be detected with various intensities in the mesenchyme, whereas Fgf1 and Fgf2 were expressed in both the epithelium and the mesenchyme. Our results indicate that FGF signaling regulates tongue development at multiple stages.

• Klíčová slova
• Expression, FGF, Papilla, Tongue,
• MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj genetika   MeSH
• epitel růst a vývoj   metabolismus   MeSH
• fibroblastové růstové faktory biosyntéza   genetika   MeSH
• hybridizace in situ MeSH
• jazyk růst a vývoj   metabolismus   MeSH
• mezoderm růst a vývoj   metabolismus   MeSH
• myši MeSH
• organogeneze genetika   MeSH
• signální transdukce MeSH
• vývojová regulace genové exprese genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH

BACKGROUND: The mouse embryonic mandible comprises two types of tooth primordia in the cheek region: progressive tooth primordia of prospective functional teeth and rudimentary tooth primordia in premolar region - MS and R2. Mice lacking Sprouty genes develop supernumerary tooth in front of the lower M1 (first molar) primordium during embryogenesis. We focused on temporal-spatial dynamics of Sonic Hedgehog expression as a marker of early odontogenesis during supernumerary tooth development. RESULTS: Using mouse embryos with different dosages of Spry2 and Spry4 genes, we showed that during the normal development of M1 in the mandible the sooner appearing Shh signaling domain of the R2 bud transiently coexisted with the later appearing Shh expression domain in the early M1 primordium. Both domains subsequently fused together to form the typical signaling center representing primary enamel knot (pEK) of M1 germ at embryonic day (E) 14.5. However, in embryos with lower Spry2;Spry4 gene dosages, we observed a non-fusion of original R2 and M1 Shh signaling domains with consequent formation of a supernumerary tooth primordium from the isolated R2 bud. CONCLUSIONS: Our results bring new insight to the development of the first lower molar of mouse embryos and define simple tooth unit capable of individual development, as well as determine its influence on normal and abnormal development of the tooth row which reflect evolutionarily conserved tooth pattern. Our findings contribute significantly to existing knowledge about supernumerary tooth formation.

• MeSH
• buněčný rodokmen MeSH
• embryo savčí MeSH
• genová dávka * MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• membránové proteiny genetika   MeSH
• myši knockoutované MeSH
• myši MeSH
• protein-serin-threoninkinasy MeSH
• proteiny hedgehog genetika   MeSH
• proteiny nervové tkáně genetika   MeSH
• zubní sklovina růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• intracelulární signální peptidy a proteiny MeSH
• membránové proteiny MeSH
• protein-serin-threoninkinasy MeSH
• proteiny hedgehog MeSH
• proteiny nervové tkáně MeSH
• Shh protein, mouse MeSH Prohlížeč
• Spry2 protein, mouse MeSH Prohlížeč
• Spry4 protein, mouse MeSH Prohlížeč