title: Feedback, Lineages and Self-Organizing Morphogenesis.
abstract: Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities.
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Sameeran
authors.initials: S
authors.lastname: Kunche
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Huaming
authors.initials: H
authors.lastname: Yan
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, United States of America.|Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Calof
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, California, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Lowengrub
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, Irvine, California, United States of America.|Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Lander
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D003198:Computer Simulation; D025461:Feedback, Physiological / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins