Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfbeta1 regulate semaphorin 3a expression in the dental mesenchyme.
During development, trigeminal nerve fibers navigate and establish their axonal projections to the developing tooth in a highly spatiotemporally controlled manner. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, we found that Sema3a regulates dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation, and that the effects of Sema3a appear to be mediated by Npn1 present in the axons. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, we found that early oral and dental epithelia, which instruct tooth formation, and epithelial Wnt4 induce Sema3a expression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers. Later, at the bud stage, epithelial Wnt4 and Tgfbeta1 regulate Sema3a expression in the dental mesenchyme. In addition, Wnt4 stimulates mesenchymal expression of Msx1 transcription factor, which is essential for tooth formation, and Tgfbeta1 proliferation of the dental mesenchymal cells. Thus, epithelial-mesenchymal interactions control Sema3a expression and may coordinate axon navigation and patterning with tooth formation. Moreover, our results suggest that the odontogenic epithelium possesses the instructive information to control the formation of tooth nerve supply.
Kettunen
Päivi
P
Division of Anatomy and Cell Biology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Løes
Sigbjørn
S
Furmanek
Tomasz
T
Fjeld
Karianne
K
Kvinnsland
Inger Hals
IH
Behar
Oded
O
Yagi
Takeshi
T
Fujisawa
Hajime
H
Vainio
Seppo
S
Taniguchi
Masahiko
M
Luukko
Keijo
K
D000818:Animals; D001369:Axons / Q000378:metabolism; D019521:Body Patterning; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D040121:Semaphorin-3A / Q000096:biosynthesis*; D013997:Time Factors; D014018:Tissue Distribution; D014070:Tooth / Q000196:embryology* / Q000294:innervation*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014276:Trigeminal Nerve / Q000502:physiology*; D051153:Wnt Proteins; D060528:Wnt4 Protein
C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D040121:Semaphorin-3A; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C555583:Wnt4 protein, rat; D020932:Nerve Growth Factor