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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE021420-02
Application #
8236886
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
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$366,938
Indirect Cost
$129,438
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
Castillo, David; Seidel, Kerstin; Salcedo, Ernesto et al. (2014) Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium. Development 141:2993-3002
Goodwin, Alice F; Tidyman, William E; Jheon, Andrew H et al. (2014) Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. Hum Mol Genet 23:682-92
Naveau, Adrien; Seidel, Kerstin; Klein, Ophir D (2014) Tooth, hair and claw: comparing epithelial stem cell niches of ectodermal appendages. Exp Cell Res 325:96-103
Harjunmaa, Enni; Seidel, Kerstin; Häkkinen, Teemu et al. (2014) Replaying evolutionary transitions from the dental fossil record. Nature 512:44-8
Li, Chun-Ying; Prochazka, Jan; Goodwin, Alice F et al. (2014) Fibroblast growth factor signaling in mammalian tooth development. Odontology 102:1-13
Chavez, Miquella G; Hu, Jimmy; Seidel, Kerstin et al. (2014) Isolation and culture of dental epithelial stem cells from the adult mouse incisor. J Vis Exp :
Michailovici, Inbal; Harrington, Heather A; Azogui, Hadar Hay et al. (2014) Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells. Development 141:2611-20
Kuang-Hsien Hu, Jimmy; Mushegyan, Vagan; Klein, Ophir D (2014) On the cutting edge of organ renewal: Identification, regulation, and evolution of incisor stem cells. Genesis 52:79-92
Goodwin, Alice F; Oberoi, Snehlata; Landan, Maya et al. (2014) Craniofacial and dental development in Costello syndrome. Am J Med Genet A 164A:1425-30
Oishi, Peter E; Klein, Ophir D; Keller, Roberta L et al. (2013) Developing physician-scientists in the fields of neonatology and pediatric critical care medicine: an effort to formulate a departmental policy. J Pediatr 163:616-7.e1

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