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Stuart A. Newman

Bio: Stuart A. Newman is an academic researcher from New York Medical College. The author has contributed to research in topics: Limb bud & Multicellular organism. The author has an hindex of 51, co-authored 194 publications receiving 7889 citations. Previous affiliations of Stuart A. Newman include Wellcome Trust Sanger Institute & Memorial Sloan Kettering Cancer Center.


Papers
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Journal ArticleDOI
TL;DR: This work proposes that the present relationship between genes and form is a highly derived condition, a product of evolution rather than its precondition, and helps to explain findings that are difficult to reconcile with the standard neo-Darwinian model.
Abstract: The close mapping between genotype and morphological phenotype in many con- temporary metazoans has led to the general notion that the evolution of organismal form is a direct consequence of evolving genetic programs. In contrast to this view, we propose that the present relationship between genes and form is a highly derived condition, a product of evolution rather than its precondition. Prior to the biochemical canalization of developmental pathways, and the stabilization of phenotypes, interaction of multicellular organisms with their physico- chemical environments dictated a many-to-many mapping between genomes and forms. These forms would have been generated by epigenetic mechanisms: initially physical processes charac- teristic of condensed, chemically active materials, and later conditional, inductive interactions among the organism's constituent tissues. This concept, that epigenetic mechanisms are the gen- erative agents of morphological character origination, helps to explain findings that are difficult to reconcile with the standard neo-Darwinian model, e.g., the burst of body plans in the early Cambrian, the origins of morphological innovation, homology, and rapid change of form. Our con- cept entails a new interpretation of the relationship between genes and biological form. J. Exp. Zool. (Mol. Dev. Evol.) 288:304-317, 2000. © 2000 Wiley-Liss, Inc.

298 citations

Journal ArticleDOI
TL;DR: It is suggested that differences in `variational properties' lead to morphostatic and morphodynamic mechanisms being represented to different extents in early and late stages of development and to their contributing in distinct ways to morphological transitions in evolution.
Abstract: We present a classification of developmental mechanisms that have been shown experimentally to generate pattern and form in metazoan organisms. We propose that all such mechanisms can be organized into three basic categories and that two of these may act as composite mechanisms in two different ways. The simple categories are cell autonomous mechanisms in which cells enter into specific arrangements ('patterns') without interacting, inductive mechanisms in which cell communication leads to changes in pattern by reciprocal or hierarchical alteration of cell phenotypes ('states') and morphogenetic mechanisms in which pattern changes by means of cell interactions that do not change cell states. The latter two types of mechanism can be combined either morphostatically, in which case inductive mechanisms act first, followed by the morphogenetic mechanism, or morphodynamically, in which case both types of mechanisms interact continuously to modify each other's dynamics. We propose that this previously unexplored distinction in the operation of composite developmental mechanisms provides insight into the dynamics of many developmental processes. In particular, morphostatic and morphodynamic mechanisms respond to small changes in their genetic and microenvironmental components in dramatically different ways. We suggest that these differences in 'variational properties' lead to morphostatic and morphodynamic mechanisms being represented to different extents in early and late stages of development and to their contributing in distinct ways to morphological transitions in evolution.

270 citations

Journal ArticleDOI
17 Aug 1979-Science
TL;DR: During development of the embryonic chick limb the skeletal pattern is laid out as cartilaginous primordia, which emerge in a proximodistal sequence over a period of 4 days, leading to sequential reorganizations of the morphogen pattern.
Abstract: During development of the embryonic chick limb the skeletal pattern is laid out as cartilaginous primordia, which emerge in a proximodistal sequence over a period of 4 days. The differentiation of cartilage is preceded by changes in cellular contacts at specific locations in the precartilage mesenchyme. Under realistic assumptions, the biosynthesis and diffusion through the extracellular matrix of a cell surface protein, such as fibronectin, will lead to spatial patterns of this molecule that could be the basis of the emergent primordia. As cellular differentiation proceeds, the size of the mesenchymal diffusion chamber is reduced in descrete steps, leading to sequential reorganizations of the morphogen pattern. The successive patterns correspond to observed rows of skeletal elements, whose emergence, in theory and in practice, depends on the maintenance of a unique boundary condition at the limb bud apex.

270 citations

Book
28 Jan 1997
TL;DR: The cell is fundamental unit of developmental systems as mentioned in this paper, and cell states include stability, oscillation, differentiation, adhesion, compartmentalization and lumen formation, and pattern formation: segmentation, axes and asymmetry.
Abstract: Introduction 1. The cell: fundamental unit of developmental systems 2. Cleavage and blastula formation 3. Cell states: stability, oscillation, differentiation 4. Cell adhesion, compartmentalization and lumen formation 5. Epithelial morphogenesis: gastrulation and neurulation 6. Mesenchymal morphogenesis 7. Pattern formation: segmentation, axes and asymmetry 8. Organogenesis 9. Fertilization: generating one living dynamical system from two 10. Evolution of developmental mechanisms Glossary References Index.

257 citations

Journal ArticleDOI
TL;DR: Using a cell-centered computational model, it is shown that the endothelial cells' elongated shape is key to correct spatiotemporal in silico replication of stable vascular network growth.

233 citations


Cited by
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Journal ArticleDOI
TL;DR: In this paper, the authors describe the rules of the ring, the ring population, and the need to get off the ring in order to measure the movement of a cyclic clock.
Abstract: 1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

3,424 citations

Journal ArticleDOI
TL;DR: This paper reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, Boolean networks and their generalizations, ordinary and partial differential equations, qualitative differential equation, stochastic equations, and so on.
Abstract: The spatiotemporal expression of genes in an organism is determined by regulatory systems that involve a large number of genes connected through a complex network of interactions. As an intuitive understanding of the behavior of these systems is hard to obtain, computer tools for the modeling and simulation of genetic regulatory networks will be indispensable. This report reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, ordinary and partial differential equations, stochastic equations, Boolean networks and their generalizations, qualitative differential equations, and rule-based formalisms. In addition, the report discusses how these formalisms have been used in the modeling and simulation of regulatory systems.

2,739 citations

01 Jan 2016
TL;DR: Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells as discussed by the authors, and the potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.
Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

1,837 citations

Journal ArticleDOI
TL;DR: Understanding the mechanisms of ECM remodeling and its regulation is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.
Abstract: The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.

1,686 citations

Journal ArticleDOI
TL;DR: Increased understanding of the induction of chondrogenic differentiation should lead to further progress in defining the mechanisms responsible for the generation of cartilaginous tissues, their maintenance, and their regeneration.
Abstract: In the adult human, mesenchymal stem cells (MSCs) resident in bone marrow retain the capacity to proliferate and differentiate along multiple connective tissue lineages, including cartilage. In this study, culture-expanded human MSCs (hMSCs) of 60 human donors were induced to express the morphology and gene products of chondrocytes. Chondrogenesis was induced by culturing hMSCs in micromass pellets in the presence of a defined medium that included 100 nM dexamethasone and 10 ng/ml transforming growth factor-beta(3) (TGF-beta(3)). Within 14 days, cells secreted an extracellular matrix incorporating type II collagen, aggrecan, and anionic proteoglycans. hMSCs could be further differentiated to the hypertrophic state by the addition of 50 nM thyroxine, the withdrawal of TGF-beta(3), and the reduction of dexamethasone concentration to 1 nM. Increased understanding of the induction of chondrogenic differentiation should lead to further progress in defining the mechanisms responsible for the generation of cartilaginous tissues, their maintenance, and their regeneration.

1,365 citations