Embryonic tongue morphogenesis in an organ culture model of mouse mandibular arches: blocking Sonic hedgehog signaling leads to microglossia.
Mouse tongue development is initiated with the formation of lateral lingual swellings just before fusion between the mediodorsal surfaces of the mandibular arches at around embryonic day 11.0. Here, we investigated the role of Sonic hedgehog (Shh) signaling in embryonic mouse tongue morphogenesis. For this, we used an organ culture model of the mandibular arches from mouse embryos at embryonic day 10.5. When the Shh signaling inhibitor jervine was added to the culture medium for 24-96 h, the formation of lateral lingual swellings and subsequent epithelial invagination into the mesenchyme were impaired markedly, leading to a hypoplastic tongue with an incomplete oral sulcus. Notably, jervine treatment reduced the proliferation of non-myogenic mesenchymal cells at the onset of forming the lateral lingual swellings, whereas it did not affect the proliferation and differentiation of a myogenic cell lineage, which created a cell community at the central circumferential region of the lateral lingual swellings as seen in vivo and in control cultures lacking the inhibitor. Thus, epithelium-derived Shh signaling stimulates the proliferation of non-myogenic mesenchymal cells essential for forming lateral lingual swellings and contributes to epithelial invagination into the mesenchyme during early tongue development.
Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Daisuke
D
Torii
Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Yuuichi
Y
Soeno
Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Kazuya
K
Fujita
Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Kaori
K
Sato
Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
Takaaki
T
Aoba
Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan. taya-yu@tky.ndu.ac.jp.
Yuji
Y
Taya
D000818:Animals; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008334:Mandible / Q000196:embryology* / Q000254:growth & development; D051379:Mice; D009024:Morphogenesis; D009924:Organ Culture Techniques; D015398:Signal Transduction; D014059:Tongue / Q000196:embryology / Q000254:growth & development*; D014060:Tongue Diseases / Q000235:genetics* / Q000473:pathology
D053823:Hedgehog Proteins; C465570:Shh protein, mouse
Epithelial invagination; Mouse embryo; Non-myogenic cell proliferation; Shh signaling; Tongue morphogenesis