The broad goal of the proposed research is to understand molecular mechanisms of tooth regeneration and tissue renewal in vertebrates. Our research benefits from explicit integration of experimental systems (cichlid fishes, zebrafish, mouse) and a unique approach translating new biology from fishes to mammals and back. In this competitive renewal application, we build on the previous project period to outline three Specific Aims that fuse unbiased and experimental approaches in multiple vertebrate tooth models to identify cell populations and molecular signals that direct natural whole-tooth replacement (cichlids and zebrafish) and mouse incisor tissue renewal. The gaps we aim to fill are significant. One in five humans presents with a genetic disorder affecting the dentition and nearly 100% develop problems (e.g, cavities) with age. 30% of people worldwide over the age of 65 lack teeth entirely. Our proposed research will provide answers to the basic question of how regenerating teeth are partitioned into coordinated zones of renewal and differentiation, and how mammalian teeth recover from damage. Insights should promote innovative strategies for bio-inspired regenerative dentistry.
The World Health Organization reports that nearly 100% of people worldwide exhibit dental defects (either genetic disorders or insults acquired with age) and that 30% of those over 65 have none of their 32 teeth remaining. Our research thus explores endogenous mechanisms of tooth regeneration and tissue renewal. Understanding natural pathways and triggers of tooth renewal will galvanize problem solving in bioengineering and may ultimately improve the lives of humans requiring dental implants.
|Ramakrishnan Varadarajan, Ajay; Mopuri, Rohini; Streelman, J Todd et al. (2018) Genome-wide protein phylogenies for four African cichlid species. BMC Evol Biol 18:1|
|An, Zhengwen; Sabalic, Maja; Bloomquist, Ryan F et al. (2018) A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors. Nat Commun 9:378|
|Bloomquist, R F; Fowler, T E; Sylvester, J B et al. (2017) A compendium of developmental gene expression in Lake Malawi cichlid fishes. BMC Dev Biol 17:3|
|Streelman, J Todd; Bloomquist, Ryan F; Fowler, Teresa E (2015) Developmental Plasticity of Patterned and Regenerating Oral Organs. Curr Top Dev Biol 115:321-33|
|Bloomquist, Ryan F; Parnell, Nicholas F; Phillips, Kristine A et al. (2015) Coevolutionary patterning of teeth and taste buds. Proc Natl Acad Sci U S A 112:E5954-62|
|Brawand, David; Wagner, Catherine E; Li, Yang I et al. (2014) The genomic substrate for adaptive radiation in African cichlid fish. Nature 513:375-381|
|Fraser, Gareth J; Bloomquist, Ryan F; Streelman, J Todd (2013) Common developmental pathways link tooth shape to regeneration. Dev Biol 377:399-414|
|Loh, Yong-Hwee E; Bezault, Etienne; Muenzel, Frauke M et al. (2013) Origins of shared genetic variation in African cichlids. Mol Biol Evol 30:906-17|
|Parnell, Nicholas F; Hulsey, C Darrin; Streelman, J Todd (2012) The genetic basis of a complex functional system. Evolution 66:3352-66|
|Loh, Yong-Hwee E; Yi, Soojin V; Streelman, J Todd (2011) Evolution of microRNAs and the diversification of species. Genome Biol Evol 3:55-65|
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