Global, circulating endocrine factors are important for coordinating differentiation and morphogenesis of numerous stem cell derived lineages during post-embryonic development and later adult homeostasis. One such factor, thyroid hormone (TH), plays a major role in the diversification and maintenance of neural-crest derived pigment cell lineages in zebrafish. Different classes of pigment cells—including black melanophores and yellow xanthophores—have markedly different responses to TH signaling. TH represses melanophore population expansion, and fish lacking TH have twice the normal number of melanophores. By contrast, TH promotes xanthophore differentiation and proliferation. We do not yet understand how this single factor, TH, differentially impacts the differentiation and morphogenesis of these cell lineages. Because TH has potentially hundreds of downstream effectors, we are taking whole-transcriptomic approaches to understand its different roles in these two cell types, including the extent to which TH specifies alternative fates of multipotent progenitors or has cell-type specific effects on morphogenesis and terminal differentiation after fates have been specified. We are also using epigenomic analyses to test whether TH differentially impacts chromatin organization in melanophore and xanthophore lineages. We anticipate that our unusually tractable system will provide novel insights into how a common endocrine signal is translated into alternative cellular outcomes across lineages during the development and maintenance of adult form.