title: Cell-autonomous and non-cell-autonomous roles for IRF6 during development of the tongue.
abstract: Interferon regulatory factor 6 (IRF6) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors. Mutations in IRF6 lead to isolated and syndromic forms of cleft lip and palate, most notably Van der Woude syndrome (VWS) and Popliteal Ptyerigium Syndrome (PPS). Mice lacking both copies of Irf6 have severe limb, skin, palatal and esophageal abnormalities, due to significantly altered and delayed epithelial development. However, a recent report showed that MCS9.7, an enhancer near Irf6, is active in the tongue, suggesting that Irf6 may also be expressed in the tongue. Indeed, we detected Irf6 staining in the mesoderm-derived muscle during development of the tongue. Dual labeling experiments demonstrated that Irf6 was expressed only in the Myf5+ cell lineage, which originates from the segmental paraxial mesoderm and gives rise to the muscles of the tongue. Fate mapping of the segmental paraxial mesoderm cells revealed a cell-autonomous Irf6 function with reduced and poorly organized Myf5+ cell lineage in the tongue. Molecular analyses showed that the Irf6-/- embryos had aberrant cytoskeletal formation of the segmental paraxial mesoderm in the tongue. Fate mapping of the cranial neural crest cells revealed non-cell-autonomous Irf6 function with the loss of the inter-molar eminence. Loss of Irf6 function altered Bmp2, Bmp4, Shh, and Fgf10 signaling suggesting that these genes are involved in Irf6 signaling. Based on these data, Irf6 plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue.
authors: Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee, United States of America. steven.goudy@vanderbilt.edu
authors: Steven
authors: S
authors: Goudy
authors: Peggi
authors: P
authors: Angel
authors: Britni
authors: B
authors: Jacobs
authors: Cynthia
authors: C
authors: Hill
authors: Veronica
authors: V
authors: Mainini
authors: Arianna L
authors: AL
authors: Smith
authors: Youssef A
authors: YA
authors: Kousa
authors: Richard
authors: R
authors: Caprioli
authors: Lawrence S
authors: LS
authors: Prince
authors: Scott
authors: S
authors: Baldwin
authors: Brian C
authors: BC
authors: Schutte
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D019070:Cell Lineage; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013947:Thymosin / Q000378:metabolism; D014059:Tongue / Q000196:embryology* / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D050835:Interferon Regulatory Factors; D013947:Thymosin; D000099201:Thymosin beta(4); C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C496464:Fgf10 protein, mouse; C528250:IRF6 protein, mouse; C465570:Shh protein, mouse; C039302:thymosin beta(10)