Multiple signaling molecules, including BMPs, FGFs, Shh, and Wnt proteins, have been implicated in mediating tissue interactions that regulate tooth initiation, morphogenesis and differentiation. In mice, the odontogenic potential, defined as the capability of an odontogenic tissue to elicit tooth developmental program in non-dental tissues, resides initially in dental epithelium, and then shifts to dental mesenchyme. Our long-term goal is to delineate the molecular basis of the odontogenic potential. Based on our previous studies, we hypothesize that during tooth initiation, BMP4 functions as an essential component of the odontogenic potential in the early dental epithelium, to induce the formation of the basal layer epithelium as well as to stimulate local cell proliferation to form a tooth bud. We further hypothesize that Wnt signaling pathway constitutes a component of the odontogenic potential in dental mesenchyme.
Two specific aims are proposed to test these hypotheses.
In Aim 1, the role of BMP4 in the early dental epithelium in tooth initiation will be defined by conditional knockout studies via the Cre/LoxP approach to achieve tissue-specific mutation of Bmp4 in the dental epithelium. This approach will also be used to delete the Bmpr-lA and Bmpr-IB genes in the dental epithelium to study if BMP4 acts intra-epithelially. Whether signaling of BMP4 to dental mesenchyme is essential for the acquisition of odontogenic potential in the mesenchyme will be tested by tissue recombination studies. Furthermore, whether Shh mediates Bmp4 activity in dental epithelium will be examined by conditional knockout and transgenic rescue experiments.
In Aim 2, if Wnt signaling acts as a critical component of the odontogenic potential in dental mesenchyme will be studied by disrupting Writ signaling pathway in tissues used for tissue recombination. This will be achieved by overexpressing Wnt antagonist sFrp3 in dental mesenchyme, and Dkk1 and a dominant negative form of Tcf in responding non-dental epithelia via microelectroporation and virus-mediated gene delivery. The potential role of Wnt5a in the induction of tooth formation by dental mesenchyme will also be tested. Lastly, whether different sFrps confer the different inductive properties to incisor and molar mesenchyme will be determined by virus-mediated gene overexpression and RNAi-mediated gene knock-down studies, together with tissue recombination and organ culture studies.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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Small, Rochelle K
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Tulane University
Anatomy/Cell Biology
Schools of Arts and Sciences
New Orleans
United States
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Wang, Y; Li, L; Zheng, Y et al. (2012) BMP activity is required for tooth development from the lamina to bud stage. J Dent Res 91:690-5
Li, Lu; Yuan, Guohua; Liu, Chao et al. (2011) Exogenous fibroblast growth factor 8 rescues development of mouse diastemal vestigial tooth ex vivo. Dev Dyn 240:1344-53
Lin, Minkui; Li, Lu; Liu, Chao et al. (2011) Wnt5a regulates growth, patterning, and odontoblast differentiation of developing mouse tooth. Dev Dyn 240:432-40
Wang, Bingmei; Li, Liwen; Du, Shengrong et al. (2010) Induction of human keratinocytes into enamel-secreting ameloblasts. Dev Biol 344:795-9
Yang, Jing; Chan, Chin Yee; Jiang, Bo et al. (2009) hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. PLoS Genet 5:e1000363
Xiong, Wei; He, Fenglei; Morikawa, Yuka et al. (2009) Hand2 is required in the epithelium for palatogenesis in mice. Dev Biol 330:131-41
Gu, Shuping; Wei, Na; Yu, Xueyan et al. (2008) Mice with an anterior cleft of the palate survive neonatal lethality. Dev Dyn 237:1509-16
Gu, Shuping; Wei, Na; Yu, Ling et al. (2008) Shox2-deficiency leads to dysplasia and ankylosis of the temporomandibular joint in mice. Mech Dev 125:729-42
He, Fenglei; Xiong, Wei; Yu, Xueyan et al. (2008) Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development 135:3871-9
Yu, Ling; Liu, Hongbing; Yan, Mingquan et al. (2007) Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton. Dev Biol 306:549-59

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