Abstract
A key issue in stem cell biology is the differentiation of homogeneous stem cells towards different fates which are also organized into desired configurations. Little is known about the mechanisms underlying the process of periodic patterning. Feather explants offer a fundamental and testable model in which multi-potential cells are organized into hexagonally arranged primordia and the spacing between primordia. Previous work explored roles of a Turing reaction-diffusion mechanism in establishing chemical patterns. Here we show that a continuum of feather patterns, ranging from stripes to spots, can be obtained when the level of p-ERK activity is adjusted with chemical inhibitors. The patterns are dose-dependent, tissue stage-dependent, and irreversible. Analyses show that ERK activity-dependent mesenchymal cell chemotaxis is essential for converting micro-signaling centers into stable feather primordia. A mathematical model based on short-range activation, long-range inhibition, and cell chemotaxis is developed and shown to simulate observed experimental results. This generic cell behavior model can be applied to model stem cell patterning behavior at large.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Patterning / drug effects
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Body Patterning / physiology*
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Butadienes
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Chemotaxis / drug effects
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Chemotaxis / physiology*
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Chick Embryo / cytology
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Chick Embryo / enzymology*
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Chick Embryo / growth & development
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Computer Simulation
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Diffusion
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / physiology*
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Feathers / cytology
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Feathers / embryology*
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Fibroblast Growth Factor 10 / pharmacology
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Fibroblast Growth Factor 4 / pharmacology
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MAP Kinase Signaling System* / drug effects
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Mesenchymal Stem Cells / drug effects
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Mesenchymal Stem Cells / enzymology
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Mesenchymal Stem Cells / physiology*
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Microscopy, Video
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Models, Biological
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Molecular Sequence Data
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Nitriles
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Phosphorylation
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Protein Processing, Post-Translational
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / physiology
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RNA Interference
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RNA, Small Interfering / pharmacology
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Specific Pathogen-Free Organisms
Substances
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Butadienes
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Fibroblast Growth Factor 10
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Fibroblast Growth Factor 4
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Nitriles
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RNA, Small Interfering
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U 0126
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Proto-Oncogene Proteins c-raf
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Extracellular Signal-Regulated MAP Kinases