Journal article
Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal
Development (Cambridge), Vol.143(22), pp.4115-4126
11/15/2016
DOI: 10.1242/dev.138883
PMCID: PMC5117215
PMID: 27660324
Abstract
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.
Details
- Title: Subtitle
- Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal
- Creators
- Zhao Sun - University of IowaWenjie Yu - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USAMaria Sanz Navarro - Developmental Biology Program, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, FinlandMason Sweat - University of IowaSteven Eliason - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USAThad Sharp - University of IowaHuan Liu - Wuhan UniversityKerstin Seidel - Department of Orofacial Sciences and Program in Craniofacial Biology, UCSF, San Francisco, CA 94143-0442, USALi Zhang - Wuhan UniversityMyriam MorenoThomas Lynch - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USANathan E Holton - Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USALaura Rogers - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USATraci Neff - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USAMichael J Goodheart - Department of Obstetrics and Gynecology, The University of Iowa, Iowa City, IA 52242, USAFrederic Michon - Developmental Biology Program, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, FinlandOphir D Klein - Department of Orofacial Sciences and Program in Craniofacial Biology, UCSF, San Francisco, CA 94143-0442, USAYang Chai - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USAAdam Dupuy - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USAJohn F Engelhardt - Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USAZhi Chen - Wuhan UniversityBrad A Amendt - Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.143(22), pp.4115-4126
- DOI
- 10.1242/dev.138883
- PMID
- 27660324
- PMCID
- PMC5117215
- NLM abbreviation
- Development
- ISSN
- 1477-9129
- eISSN
- 1477-9129
- Publisher
- England
- Grant note
- R01 DE013941 / NIDCR NIH HHS U24 DE026914 / NIDCR NIH HHS R01 DK047967 / NIDDK NIH HHS P30 CA086862 / NCI NIH HHS R37 DE012711 / NIDCR NIH HHS
- Language
- English
- Date published
- 11/15/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Orthodontics; Anthropology; Anatomy and Cell Biology; Pathology; Radiation Oncology; Craniofacial Anomalies Research Center; Obstetrics and Gynecology; Dental Research; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9983930392602771
Metrics
27 Record Views