title: Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation.
abstract: 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.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. lochovska@biomed.cas.cz.|Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic. lochovska@biomed.cas.cz.
authors.forename: Katerina
authors.initials: K
authors.lastname: Lochovska
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. repete@biomed.cas.cz.
authors.forename: Renata
authors.initials: R
authors.lastname: Peterkova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. pavlikova@biomed.cas.cz.|Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic. pavlikova@biomed.cas.cz.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Pavlikova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. marhor@biomed.cas.cz.
authors.forename: Maria
authors.initials: M
authors.lastname: Hovorakova
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003743:Dental Enamel / Q000254:growth & development*; D004622:Embryo, Mammalian; D018628:Gene Dosage; D053823:Hedgehog Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; C499037:Spry4 protein, mouse; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse