Regenerative processes are poorly understood. This proposal aims to expand scientific understanding of how regeneration occurs in vertebrate limbs. In urodele amphibians, regeneration of a lost limb is thought to occur by dedifferentiation of remaining tissues to create a blastema, followed by cell proliferation and patterning events that direct the redifferentiation of cells to create components of the new limb.
In Aim 1 of this proposal, individual cell lineages within a regenerating axolotl limb will be traced to determine the source of cells used for dedifferentiation and the fate of these cells within the new limb. The potential contribution of stem cells to limb regeneration in mammals will be explored in Aim 2. In mammals, limb regeneration is restricted to digit tips and becomes increasingly restricted distally with age.
Aim 2 will test the hypothesis that a specific set of stem cells, msxl-expressing cells, found at the digit tips confers regenerative ability. Testing this hypothesis will involve transplanting msxl cells to more proximal locations and determining if they can induce regeneration there. If so, can the cells be manipulated to allow regeneration of proximal elements? ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD054082-02
Application #
7286356
Study Section
Special Emphasis Panel (ZRG1-F05-J (20))
Program Officer
Javois, Lorette Claire
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$45,976
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Whited, Jessica L; Tsai, Stephanie L; Beier, Kevin T et al. (2013) Pseudotyped retroviruses for infecting axolotl in vivo and in vitro. Development 140:1137-46
Whited, Jessica L; Lehoczky, Jessica A; Tabin, Clifford J (2012) Inducible genetic system for the axolotl. Proc Natl Acad Sci U S A 109:13662-7
Whited, Jessica L; Lehoczky, Jessica A; Austin, Christina A et al. (2011) Dynamic expression of two thrombospondins during axolotl limb regeneration. Dev Dyn 240:1249-58
Whited, Jessica L; Tabin, Clifford J (2009) Limb regeneration revisited. J Biol 8:5