The central tenet of regenerative medicine is to unlock the genetic programs that promote natural tissue regeneration. However, a major roadblock to achieving this reality is our lack of understanding of the genetic mechanisms that underscore complex tissue regeneration. Appendages -limbs, tail, and fins -are the most studied model organs in non-mammalian regeneration research based on the accessibility of the organs, as well as the efficiency and near perfection of restoration of a three-dimensional tissue comprised of many cell types. While appendage regeneration in mammals is restricted to the distal tips of digits, the zebrafish has maintained an enhanced capacity to regenerate multiple appendage tissues, including bone, nerves, blood vessels, epidermis and pigment cells. Our research program exploits the experimental and genetic prowess of the zebrafish to address two fundamental questions that underscore appendage regeneration. What molecular pathways regulate the natural cellular reprogramming from differentiated, quiescent tissues into highly proliferative, regenerative cells in response to injury? Is there is a core regulatory cascade that defines regenerative outgrowth and patterning during tissue replacement. Specifically, we will test the hypothesis that microRNAs play key roles in the initiation and maintenance of proliferative progenitor tissue during appendage regeneration. Understanding which specific molecular programs by which nonmammalian vertebrate model systems faithfully regrow complex organs will provide the basis for potential regenerative therapies.

Public Health Relevance

Our studies are significant and innovative because we will elucidate the genetic foundation that drives natural cellular reprogramming and tissue replacement during appendage regeneration. These studies will enhance potential therapies to aid wound healing and repair in humans and provide perspective for changing the existing limitations in regenerative capacity of most human organs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM104318-01
Application #
8465639
Study Section
Special Emphasis Panel (ZGM1-TWD-B (CB))
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$354,991
Indirect Cost
$149,794
Name
Mount Desert Island Biological Lab
Department
Type
DUNS #
077470003
City
Salsbury Cove
State
ME
Country
United States
Zip Code
04672
Wu, Cheng-Wei; Deonarine, Andrew; Przybysz, Aaron et al. (2016) The Skp1 Homologs SKR-1/2 Are Required for the Caenorhabditis elegans SKN-1 Antioxidant/Detoxification Response Independently of p38 MAPK. PLoS Genet 12:e1006361
Soundararajan, Ramani; Stearns, Timothy M; Czachor, Alexander et al. (2016) Global gene profiling of aging lungs in Atp8b1 mutant mice. Aging (Albany NY) 8:2232-2252
Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D et al. (2016) Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish. Proc Natl Acad Sci U S A 113:E2189-98
Rizzo, Francesca; Coffman, James A; Arnone, Maria Ina (2016) An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo. Dev Biol 416:173-86
King, Benjamin L; Yin, Viravuth P (2016) A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration. PLoS One 11:e0157106
Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J et al. (2016) The Comparative Toxicogenomics Database: update 2017. Nucleic Acids Res :
King, Benjamin L; Shi, Ling Fang; Kao, Peter et al. (2016) Calcium activated K⁺ channels in the electroreceptor of the skate confirmed by cloning. Details of subunits and splicing. Gene 578:63-73
Grondin, Cynthia J; Davis, Allan Peter; Wiegers, Thomas C et al. (2016) Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database. Environ Health Perspect 124:1592-1599
Yamada, Toshiki; Krzeminski, Mickael; Bozoky, Zoltan et al. (2016) Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel. Biophys J 111:1876-1886
Hartig, Ellen I; Zhu, Shusen; King, Benjamin L et al. (2016) Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation. Biol Open 5:1134-41

Showing the most recent 10 out of 36 publications