Advances in regenerative medicine offer great potential for the treatment of limb amputees. However, despite an increasing understanding of the molecular mechanisms underlying regenerative responses in model systems (e.g., salamander limb regeneration), the application of this knowledge to mammalian systems is lagging. With the ultimate goal of inducing mammalian limb regeneration, we propose here to apply the results gained from recent studies on the wound epidermis formed during salamander limb regeneration to a non-regenerative system, i.e., mouse digit amputation wounds. Specifically, we hypothesize that the murine orthologs of those genes and microRNAs identified in regenerating salamander limbs can initiate mammalian regeneration when ectopically expressed. If successful, the basic knowledge gained from these unprecedented studies will have a significant impact on tissue repair, wound healing and comparative developmental biology. Moreover, this work will provide the foundation for future human limb regeneration clinical applications.

Public Health Relevance

Advances in regenerative medicine offer great potential for the treatment of limb amputees. However, despite an increasing understanding of the molecular mechanisms underlying regenerative responses in model systems (e.g., salamander limb regeneration), the application of this knowledge to mammalian systems is lagging. With the ultimate goal of inducing mammalian limb regeneration, we propose here to apply the results gained from recent studies on the wound epidermis formed during salamander limb regeneration to a non-regenerative system, i.e., mouse digit amputation wounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM094944-04
Application #
8536848
Study Section
Special Emphasis Panel (ZGM1-GDB-7 (EU))
Program Officer
Haynes, Susan R
Project Start
2010-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$318,132
Indirect Cost
$127,062
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Campbell, Leah J; Suarez-Castillo, Edna C; Ortiz-Zuazaga, Humberto et al. (2011) Gene expression profile of the regeneration epithelium during axolotl limb regeneration. Dev Dyn 240:1826-40