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Development. 2016 Nov 15;143(22):4115-4126. Epub 2016 Sep 22.

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal.

Author information

1
Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USA.
2
Developmental Biology Program, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
3
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, P.R.China.
4
Department of Orofacial Sciences and Program in Craniofacial Biology, UCSF, San Francisco, CA 94143-0442, USA.
5
Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
6
Department of Obstetrics and Gynecology, The University of Iowa, Iowa City, IA 52242, USA.
7
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
8
Department of Anatomy and Cell Biology, and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USA brad-amendt@uiowa.edu.

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.

KEYWORDS:

Cleft palate; Lef-1; Periderm; Pitx2; Sox2; Stem cells

PMID:
27660324
PMCID:
PMC5117215
DOI:
10.1242/dev.138883
[Indexed for MEDLINE]
Free PMC Article

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