The growth, repair or maintenance of mature tissues often involves recruitment of new cells from stem cell precursors. In zebrafish, the melanocytes of the pigment pattern are supported by stem cells that are recruited during developmental transitions, growth of the animal or following experimental ablation in larvae or adults. Our goal is to understand the mechanisms involved in recruiting stem cells to re-enter developmental pathways, or hold stem cells in check when they are not needed. To this goal, we will investigate how melanocyte stem cells divide following chemical ablation of larval melanocytes, and investigate how genetically distinct melanocytes are related through stem cell labeling. Mutagenesis screens have identified two melanocyte regenerationspecific mutants, eartha (gfptl) and Julie (skiv2!2). We will investigate how these mutations block development of melanocyte precursors, and generate temperature-dependent alleles to assess their roles in various melanocyte stem cell driven processes. These mutants will also let us investigate how different precursor states feedback on the melanocyte stem cell to keep it quiescent. Finally, we will continue our successful pilot screen to identify novel melanocyte regeneration mutants. This work will have a general impact in understanding the roles that regulate adult stem cells. It will identify key genes involved in orchestrating recruitment of stem cells during development, or during homeostasis. Understanding the mechanisms that regulate stem cells will help guide efforts to reconstitute organs in vivo and in vitro, and also provide insights into the growth control mechanisms defective in cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56GM056988-10
Application #
7464769
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Haynes, Susan R
Project Start
1998-01-01
Project End
2008-07-31
Budget Start
2007-08-06
Budget End
2008-07-31
Support Year
10
Fiscal Year
2007
Total Cost
$406,319
Indirect Cost
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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