Some of the most important problems facing biology today involve the mechanisms by which post-embryonic stem cells are established, maintained, and ultimately recruited to differentiate at particular times and places in the adult. These cells are essential for normal development, and understanding their biology has translational importance in the context of cancer, senescence and tissue regeneration.
We use post-embryonic lineages of pigment cells to understand fundamental aspects of stem cell biology. These cells arise from the neural crest, which also contributes to numerous other tissues and organs, including neurons and glia of the peripheral nervous system and bone and cartilage of the craniofacial skeleton. Our work has identified different lineages of neural crest derived pigment cells with distinct behaviors and requirements.
Adult melanophore and iridophore stem cells
Melanophores are homologous to mammalian melanocytes and develop using the same genetic pathways. We showed that latent precursors to adult melanophores are found within the peripheral nervous system (as in mammals) and that these cells migrate to the skin beginning ~10 d post fertilization. ErbB receptor tyrosine kinase signaling is required to establish these stem cells, and we have identified several genes needed for their later recruitment, including puma, which encodes an alpha tubulin. Precursors to iridophores are also found within the peripheral nervous system.
Development of adult melanophores (left) fails in the puma mutant (right)
over 18 h
migrating to the skin
Precursor detaching from peripheral nerve
Lineages of adult pigment cells.
A different origin of adult xanthophores and the differential dependence of adult pigment cell lineages on thyroid hormone
In contrast to melanophores and iridophores, we showed that many adult xanthophores develop directly from embryonic xanthophores, which transiently lose their pigment, proliferate, and ultimate re-differentiate during adult pattern formation. Using transgenic and mutational approaches we showed that thyroid hormone promotes xanthophore differentation and proliferation. Yet, thyroid hormone has the opposite effect on melanophores, repressing the adult melanophore population. Normal pigment cell lineage development, and pattern formation, are thus critically dependent on the right balance of thyroid hormone.
Excess xanthophore division in hyperthyroid mutant
Current projects include
Department of Biology
University of Virginia
Physical and Life Sciences Building
Charlottesville VA 22904
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