Abstract

Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. Additionally, tooth anomalies are common in many craniofacial syndromes, and the easy accessibility of the oral cavity makes teeth an excellent test case for organ replacement. A thorough understanding of the molecular processes that drive tooth renewal and regeneration will be crucial to efforts to build new teeth. We are using the mouse incisor as a model for understanding the mechanisms that underlie the ability of stem cells to contribute to renewal of dental tissues, because it grows continuously due to the presence of adult stem cells. In this application, we propose to learn about the role of transcriptional control of stem cell-driven tooth renewal in the mouse incisor by focusing on how Bmi1 regulates this process. Bmi1 is a Polycomb Group (PcG) protein that is required for stem cell self-renewal in multiple tissues. The experiments proposed in the application will first identify which differentiated cell types in the incisor arise from Bmi1- expressing stem cells using genetic lineage tracing approaches. Next, we will explore the functional role of Bmi1 in incisor stem cell self-renewal and differentiation in vivo and in vitro. Finally, we will identify genetic targets of Bmi1 and determine their function in dental stem cells. These studies will advance our understanding of how nature normally uses stem cells in dental regeneration. Such information will inform future efforts aimed at stem cell-based tooth bioengineering.

Public Health Relevance

Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. A thorough understanding of the molecular processes that drive tooth regeneration will be crucial to efforts to build new teeth. We propose to learn about the natural role of transcriptional control of stem cell- driven tooth renewal by focusing on how a gene called Bmi1 regulates this process. For these studies, we will use the rodent incisor as a model system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
3R01DE021420-03S1
Application #
8736083
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Lumelsky, Nadya L
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2013-08-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$69,326
Indirect Cost
$25,169

  Institution

Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Naveau, Adrien; Zhang, Bin; Meng, Bo et al. (2017) Isl1 Controls Patterning and Mineralization of Enamel in the Continuously Renewing Mouse Incisor. J Bone Miner Res 32:2219-2231
Du, Wen; Prochazka, Jan; Prochazkova, Michaela et al. (2016) Expression of FGFs during early mouse tongue development. Gene Expr Patterns 20:81-7
Tapaltsyan, Vagan; Charles, Cyril; Hu, Jianxin et al. (2016) Identification of novel Fgf enhancers and their role in dental evolution. Evol Dev 18:31-40
Jheon, Andrew H; Prochazkova, Michaela; Meng, Bo et al. (2016) Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects. J Bone Miner Res 31:152-62
Koledova, Zuzana; Zhang, Xiaohong; Streuli, Charles et al. (2016) SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling. Proc Natl Acad Sci U S A 113:E5731-40
Tapaltsyan, Vagan; Eronen, Jussi T; Lawing, A Michelle et al. (2015) Continuously growing rodent molars result from a predictable quantitative evolutionary change over 50 million years. Cell Rep 11:673-80
Goodwin, Alice F; Kim, Rebecca; Bush, Jeffrey O et al. (2015) From Bench to Bedside and Back: Improving Diagnosis and Treatment of Craniofacial Malformations Utilizing Animal Models. Curr Top Dev Biol 115:459-92
Prochazka, Jan; Prochazkova, Michaela; Du, Wen et al. (2015) Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis. Dev Cell 35:713-24
Jheon, Andrew H; Prochazkova, Michaela; Sherman, Michael et al. (2015) Spontaneous emergence of overgrown molar teeth in a colony of Prairie voles (Microtus ochrogaster). Int J Oral Sci 7:23-6
Marangoni, Pauline; Charles, Cyril; Tafforeau, Paul et al. (2015) Phenotypic and evolutionary implications of modulating the ERK-MAPK cascade using the dentition as a model. Sci Rep 5:11658

Showing the most recent 10 out of 36 publications