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Deciphering principles of morphogenesis from temporal and spatial patterns on the integument
Authors:Ang Li  Yung‐Chih Lai  Seth Figueroa  Tian Yang  Randall B. Widelitz  Krzysztof Kobielak  Qing Nie  Cheng Ming Chuong
Affiliation:1. Department of Pathology, University of Southern California, Los Angeles, California;2. Center for Developmental Biology and Regenerative Medicine, Taiwan University, Taipei, Taiwan;3. Department of Biomedical Engineering, University of California, Irvine, California;4. Department of Cell Biology, College of Basic Medicine, Third Military Medical University, Chongqing, China;5. Department of Mathematics, University of California, Irvine, California;6. Stem Cell and Regenerative Medicine Center, China Medical University, Taichung, Taiwan
Abstract:Background : How tissue patterns form in development and regeneration is a fundamental issue remaining to be fully understood. The integument often forms repetitive units in space (periodic patterning) and time (cyclic renewal), such as feathers and hairs. Integument patterns are visible and experimentally manipulatable, helping us reveal pattern formative processes. Variability is seen in regional phenotypic specificities and temporal cycling at different physiological stages. Results: Here we show some cellular/molecular bases revealed by analyzing integument patterns. (1) Localized cellular activity (proliferation, rearrangement, apoptosis, differentiation) transforms prototypic organ primordia into specific shapes. Combinatorial positioning of different localized activity zones generates diverse and complex organ forms. (2) Competitive equilibrium between activators and inhibitors regulates stem cells through cyclic quiescence and activation. Conclusions: Dynamic interactions between stem cells and their adjacent niche regulate regenerative behavior, modulated by multi‐layers of macro‐environmental factors (dermis, body hormone status, and external environment). Genomics studies may reveal how positional information of localized cellular activity is stored. In vivo skin imaging and lineage tracing unveils new insights into stem cell plasticity. Principles of self‐assembly obtained from the integumentary organ model can be applied to help restore damaged patterns during regenerative wound healing and for tissue engineering to rebuild tissues. Developmental Dynamics 244:905–920, 2015. © 2015 Wiley Periodicals, Inc.
Keywords:stem cells  hairs  feathers  pattern formation  self‐organization  regeneration  hair cycle  systems biology  molecular circuit  modularity
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