![]() Zebrafish skin, like all vertebrate skin, has a superficial epidermis composed of ectoderm-derived epithelial cells and an underlying dermis composed of mesoderm-derived mesenchymal cells and collagenous stromal matrix ( Le Guellec et al., 2004 Aman and Parichy, 2020). Zebrafish ( Danio rerio) is an outstanding research organism for studying vertebrate skin patterning and morphogenesis. To these ends, the development of skin, and cell types within the skin, have been studied across a variety of research organisms, yielding insights into both general and species-specific mechanisms ( Duverger and Morasso, 2009 Chen et al., 2015 Patterson and Parichy, 2019 Aman and Parichy, 2020). Comparing developmental mechanisms across species can provide clues to the origin and evolution of this important organ system and may also reveal fundamental mechanisms relevant to human health and disease. Studying the skin of research organisms chosen based on phylogeny or experimental exigency can improve our understanding of regulatory mechanisms underlying integumental patterning and morphogenesis. Additionally, while human skin is a major contributor to our outward appearance, bears all our physical interactions, and detects all our tactile sensations, it remains a failure-prone organ system with numerous poorly understood and debilitating pathologies. Understanding the mechanistic underpinnings of animal form and phenotypic diversity is an enduring goal of basic biology and studying skin patterning and morphogenesis can advance that goal. Providing this boundary function and serving as the primary interface between organisms and their environments are sophisticated integuments that, in vertebrates, comprise marvelous and varied skins, decorated with patterns of pigmentation and arrayed appendages including feathers, fur or scales. The steady-state chemistry of life on earth occurs within compartments bounded from the rest of the cosmos. The reviewers have suggestions for clarifications and acknowledging caveats to some experiments, but overall assess the significance of the manuscript to be fundamental and the quality of the data compelling. These data are used by the authors to develop and test hypotheses about cell lineage relationships and signaling interactions between cell types in the skin, allowing them to identify roles for several signaling pathways and the hypodermis in scale and pigment cell development. This study provides a clearly presented and thoughtfully analyzed single cell-resolution dataset of gene expression in wildtype and mutant zebrafish skin. Additionally, these comprehensive single-cell transcriptomic data representing skin phenotypes of biomedical relevance should provide a useful resource for accelerating discovery of mechanisms that govern skin development and homeostasis. These data reveal a previously undescribed population of epidermal cells that express transcripts encoding enamel matrix proteins, suggest hormonal control of epithelial-mesenchymal signaling, clarify the signaling network that governs scale papillae development, and identify a critical role for the hypodermis in supporting pigment cell development. To learn about cell types and signaling interactions that govern skin patterning and morphogenesis we generated and analyzed single cell transcriptomes of skin from wild-type fish as well as fish having genetic or transgenically induced defects in squamation or pigmentation. ![]() ![]() Understanding mechanisms that regulate stripe patterning and scale morphogenesis may lead to discovery of fundamental mechanisms that govern development of animal form. ![]() In zebrafish, regularly patterned pigment stripes and an array of calcified scales form simultaneously in the skin during post-embryonic development. Pigment patterns and skin appendages are prominent features of vertebrate skin. ![]()
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