Pavan, William ("Bill") (NHGRI)
This technology includes transgenic mice to be used in the study of melanocyte stem cells (MSCs) for utilization in regenerative medicine. Using the melanocyte system as a model, we investigated establishment of MSCs in the hair bulge - the stem cell compartment of the hair. During embryogenesis, all melanoblasts express SOX10, but this expression is downregulated during hair follicle morphogenesis and MSC differentiation. To further study the role of SOX10, we generated transgenic mice overexpressing SOX10 in melanoblasts. In these mice, named Tg(DctSox10), SOX10 expression was controlled by the minimal promoter of dopachrome tautomerase (DCT), a gene whose protein product functions to regulate pigment synthesis and is used as a melanoblast marker. We found that SOX10 overexpression in the melanoblasts of Tg(DctSox10) heterozygous mice results in aberrant differentiation and ectopic pigmentation of cells residing in the hair bulge. Furthermore, Tg(DctSox10) homozygotes exhibit premature hair graying, attributable to the absence of MSCs and the consequential loss of melanocyte progeny that localize to the hair bulb.
- Understanding the etiology of stem cells during development could aid in their use in regenerative medicine and in diseases where cells exhibit stem cell-like characteristics.
- Studying the factors regulating melanocyte development could add to the understanding of the complex transition of melanocytes into melanoma cells and the progression of this cancer.
Potential to be used in regenerative medicine and in diseases with cells with stem cell-like characteristics.