Growth, repair and homeostasis of adult tissues suggests that they are monitored and maintained by adult, or quiescent, stem cells. In turn, growth control of the quiescent stem cell requires mechanisms whereby their target tissues keep them in check, allowing stem cell activation when needed. We use developmental and genetic analysis to explore these mechanisms in the zebrafish melanocyte pigment pattern. In this proposal, we take advantage of chemically-induced melanocyte-ablation followed by larval melanocyte regeneration to explore mechanisms of quiescent stem cell growth control. Analyses include (i) BrdU incorporation to study growth histories and relationships of stem cell populations and clonal analysis of GFP expression in mosaic animals, (ii) identification of mutants that are specifically defective for melanocyte regeneration, and identification of the mutated gene, and (iii) whether or how mutant target tissues suppress or keep their sustaining stem cells in check. Thus, this proposal will provide novel insights into the developmental and genetic mechanisms of growth control of quiescent or adult stem cells that will in turn facilitate our ability to harness them for medical applications. Using embryonic or adult stem cells in regenerative medicine to replace damaged or missing tissues requires that we know and can manipulate the signals that act to recruit or drive the stem cells to differentiate, or act to repress their development. We use melanocyte regeneration in zebrafish to identify the developmental and genetic mechanisms that regulate the melanocyte stem cell, towards understanding the general mechanisms that positively and negatively regulate stem cell development in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056988-13
Application #
8111228
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Haynes, Susan R
Project Start
1998-01-01
Project End
2013-06-04
Budget Start
2011-08-01
Budget End
2013-06-04
Support Year
13
Fiscal Year
2011
Total Cost
$372,438
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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