Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal.
Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development.
['Sun|Zhao|Z|', 'Yu|Wenjie|W|', 'Sanz Navarro|Maria|M|', 'Sweat|Mason|M|', 'Eliason|Steven|S|', 'Sharp|Thad|T|', 'Liu|Huan|H|', 'Seidel|Kerstin|K|', 'Zhang|Li|L|', 'Moreno|Myriam|M|', 'Lynch|Thomas|T|', 'Holton|Nathan E|NE|', 'Rogers|Laura|L|', 'Neff|Traci|T|', 'Goodheart|Michael J|MJ|', 'Michon|Frederic|F|', 'Klein|Ophir D|OD|', 'Chai|Yang|Y|', 'Dupuy|Adam|A|', 'Engelhardt|John F|JF|', 'Chen|Zhi|Z|', 'Amendt|Brad A|BA|0000-0001-6524-1006']
D000818:Animals D000066673:Cell Self Renewal D002478:Cells, Cultured D004622:Embryo, Mammalian D004848:Epithelium D018507:Gene Expression Regulation, Developmental D053263:Gene Regulatory Networks D018398:Homeodomain Proteins D007180:Incisor D051821:Lymphoid Enhancer-Binding Factor 1 D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009805:Odontogenesis D011485:Protein Binding D055748:SOXB1 Transcription Factors D013234:Stem Cells D014157:Transcription Factors
Sox2 Lef-1 Pitx2 Stem cells Cleft palate Periderm