title: BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth.
abstract: During embryogenesis, ectodermal stem cells adopt different fates and form diverse ectodermal organs, such as teeth, hair follicles, mammary glands, and salivary glands. Interestingly, these ectodermal organs differ in their tissue homeostasis, which leads to differential abilities for continuous growth postnatally. Mouse molars lose the ability to grow continuously, whereas incisors retain this ability. In this study, we found that a BMP-Smad4-SHH-Gli1 signaling network may provide a niche supporting transient Sox2+ dental epithelial stem cells in mouse molars. This mechanism also plays a role in continuously growing mouse incisors. The differential fate of epithelial stem cells in mouse molars and incisors is controlled by this BMP/SHH signaling network, which partially accounts for the different postnatal growth potential of molars and incisors. Collectively, our study highlights the importance of crosstalk between two signaling pathways, BMP and SHH, in regulating the fate of epithelial stem cells during organogenesis.
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA; Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, PRC.
authors: Jingyuan
authors: J
authors: Li
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
authors: Jifan
authors: J
authors: Feng
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA; Department of Prosthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing 100081, PRC.
authors: Yang
authors: Y
authors: Liu
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
authors: Thach-Vu
authors: TV
authors: Ho
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
authors: Weston
authors: W
authors: Grimes
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
authors: Hoang Anh
authors: HA
authors: Ho
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
authors: Shery
authors: S
authors: Park
authors: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, PRC.
authors: Songlin
authors: S
authors: Wang
authors: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ychai@usc.edu.
authors: Yang
authors: Y
authors: Chai
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000096:biosynthesis; D053823:Hedgehog Proteins / Q000378:metabolism*; D007180:Incisor / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008963:Molar / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D009805:Odontogenesis; D051881:Receptor, Notch1 / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D000071676:Zinc Finger Protein GLI1
chemical_list: D019485:Bone Morphogenetic Proteins; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D055748:SOXB1 Transcription Factors; C465570:Shh protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; C527783:Sox2 protein, mouse; D000071676:Zinc Finger Protein GLI1; D016695:Glycosyltransferases; C498392:Lfng protein, mouse