Stem cells are critical in normal development and understanding their biology is essential for a fuller understanding of tissue senescene and regenerative potential, as well as many types of neoplasia. The long-term goal of this project is to understand the mechanisms by which stem cells are established during embryogenesis, maintained during post-embryonic development, and then recruited to differentiate at particular times and places both in the developing adult and during regeneration. This work exploits the post-embryonic development of zebrafish melanophores, homologues of mammalian melanocytes, as an especially tractable system for studying stem and progenitor cell biology, with the potential to identify common and essential features of stem cell systems more generally. Studies in Aim 1 will test mechanisms required during embryogenesis to establish precursors to post-embryonic melanophores that will differentiate only weeks or months later, with particular emphasis on ErbB signaling and roles played by embryonic melanophore and glial lineages. The experiments proposed in Aim 2 focus on the morphogenetic behaviors and niches of melanophore stem cells and their progeny during later post-embryonic development, and whether genetically independent pools of progenitors contribute to the adult complement of melanophores. Finally, Aim 3 addresses a later phase in this lineage, when stem cells are recruited to differentiate as melanophores, and how the local tissue environment affects the survival and migration of these cells, here dissecting roles for a novel gene, basonuclin-2, likely required for skin development and homeostasis, as well as the expression of trophic factors required by adult melanophores. Together, these studies will answer several critical questions about this post-embryonic, stem-cell dependent lineage, and will be relevant to a variety of other stem cell systems in zebrafish and mammalian development, as well as in human disease.
Pigment cells in human are associated with a variety of pigmentary disorders ranging from vitiligo to melanoma. Developing therapeutic interventions for such disorders required understanding the basic biology of these cells, and particularly, the stem cell precursors from which they originate. Our research will provide new insights into the establishment, maintenance, and recruitment of stem cells for zebrafish post-embryonic pigment cells, and in so doing, will contribute to our understanding of shared mechanisms and essential features of stem cell systems, with potential relevance to the human disease, regeneration, and tissue senescence.
|McMenamin, Sarah K; Bain, Emily J; McCann, Anna E et al. (2014) Thyroid hormone-dependent adult pigment cell lineage and pattern in zebrafish. Science 345:1358-61|
|Patterson, Larissa B; Bain, Emily J; Parichy, David M (2014) Pigment cell interactions and differential xanthophore recruitment underlying zebrafish stripe reiteration and Danio pattern evolution. Nat Commun 5:5299|
|Inoue, Shinya; Kondo, Shigeru; Parichy, David M et al. (2014) Tetraspanin 3c requirement for pigment cell interactions and boundary formation in zebrafish adult pigment stripes. Pigment Cell Melanoma Res 27:190-200|
|Hamada, Hiroki; Watanabe, Masakatsu; Lau, Hiu Eunice et al. (2014) Involvement of Delta/Notch signaling in zebrafish adult pigment stripe patterning. Development 141:318-24|
|Patterson, Larissa B; Parichy, David M (2013) Interactions with iridophores and the tissue environment required for patterning melanophores and xanthophores during zebrafish adult pigment stripe formation. PLoS Genet 9:e1003561|
|McMenamin, Sarah K; Minchin, James E N; Gordon, Tiffany N et al. (2013) Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini. Endocrinology 154:1476-87|
|Budi, Erine H; Patterson, Larissa B; Parichy, David M (2011) Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation. PLoS Genet 7:e1002044|
|Larson, Tracy A; Gordon, Tiffany N; Lau, Hiu E et al. (2010) Defective adult oligodendrocyte and Schwann cell development, pigment pattern, and craniofacial morphology in puma mutant zebrafish having an alpha tubulin mutation. Dev Biol 346:296-309|
|Lang, Michael R; Patterson, Larissa B; Gordon, Tiffany N et al. (2009) Basonuclin-2 requirements for zebrafish adult pigment pattern development and female fertility. PLoS Genet 5:e1000744|
|Christiansen, Helena E; Lang, Michael R; Pace, James M et al. (2009) Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth. PLoS One 4:e8481|
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