Nuclear Shape, Mechanics, and Mechanotransduction [2008;102:1307–1318] Emerin and the Nuclear Lamina in Muscle and Cardiac Disease [2008;103:16–23] Mechanical Control of Tissue Morphogenesis

Mechanical forces participate in morphogenesis from the level of individual cells to whole organism patterning. This article reviews recent research that has identified specific roles for mechanical forces in important developmental events. One well defined example is that dynein-driven cilia create fluid flow that determines left-right patterning in the early mammalian embryo. Fluid flow is also important for vasculogenesis, and evidence suggests that fluid shear stress rather than fluid transport is primarily required for remodeling the early vasculature. Contraction of the actin cytoskeleton, driven by nonmuscle myosins and regulated by the Rho family GTPases, is a recurring mechanism for controlling morphogenesis throughout development, from gastrulation to cardiogenesis. Finally, novel experimental approaches suggest critical roles for the actin cytoskeleton and the mechanical environment in determining differentiation of mesenchymal stem cells. Insights into the mechanisms linking mechanical forces to cell and tissue differentiation pathways are important for understanding many congenital diseases and for developing regenerative medicine strategies.

[1]  R. Adelstein,et al.  Nonmuscle myosin II moves in new directions , 2008, Journal of Cell Science.

[2]  Lance A Davidson,et al.  Variation and robustness of the mechanics of gastrulation: the role of tissue mechanical properties during morphogenesis. , 2007, Birth defects research. Part C, Embryo today : reviews.

[3]  Scott E Fraser,et al.  Vascular remodeling of the mouse yolk sac requires hemodynamic force , 2007, Development.

[4]  Michael Kücken,et al.  Models for fingerprint pattern formation. , 2007, Forensic science international.

[5]  T. Lecuit,et al.  Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis , 2007, Nature Reviews Molecular Cell Biology.

[6]  W. Bloch,et al.  Endothelial precursor cell migration during vasculogenesis. , 2007, Circulation research.

[7]  Roger R Markwald,et al.  Transitions in Early Embryonic Atrioventricular Valvular Function Correspond With Changes in Cushion Biomechanics That Are Predictable by Tissue Composition , 2007, Circulation research.

[8]  E. Portales-Casamar,et al.  M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion. , 2007, Molecular biology of the cell.

[9]  M. Shen Nodal signaling: developmental roles and regulation , 2007, Development.

[10]  M. Blum,et al.  Cilia-Driven Leftward Flow Determines Laterality in Xenopus , 2007, Current Biology.

[11]  Melody A Swartz,et al.  A driving force for change: interstitial flow as a morphoregulator. , 2007, Trends in cell biology.

[12]  Michelle Peckham,et al.  Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse , 2006, Journal of Cell Science.

[13]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[14]  Roles and regulation , 2006, Veterinary Record.

[15]  M. Spector,et al.  Effects of cross-linking type II collagen-GAG scaffolds on chondrogenesis in vitro: dynamic pore reduction promotes cartilage formation. , 2006, Tissue engineering.

[16]  G. Falcone,et al.  Fine Regulation of RhoA and Rock Is Required for Skeletal Muscle Differentiation* , 2006, Journal of Biological Chemistry.

[17]  F. Beier,et al.  RhoA/ROCK Signaling Regulates Chondrogenesis in a Context-dependent Manner* , 2006, Journal of Biological Chemistry.

[18]  David F Meaney,et al.  Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures. , 2006, Biophysical journal.

[19]  S. Noselli,et al.  Type ID unconventional myosin controls left–right asymmetry in Drosophila , 2006, Nature.

[20]  K. Matsuno,et al.  An unconventional myosin in Drosophila reverses the default handedness in visceral organs , 2006, Nature.

[21]  T. Reed,et al.  High heritability of fingertip arch patterns in twin‐pairs , 2006, American journal of medical genetics. Part A.

[22]  Donald E Ingber,et al.  Mechanical control of tissue morphogenesis during embryological development. , 2006, The International journal of developmental biology.

[23]  Josef D. Franke,et al.  Nonmuscle Myosin II Generates Forces that Transmit Tension and Drive Contraction in Multiple Tissues during Dorsal Closure , 2005, Current Biology.

[24]  Lei Zhao,et al.  Modulation of Muscle Regeneration, Myogenesis, and Adipogenesis by the Rho Family Guanine Nucleotide Exchange Factor GEFT , 2005, Molecular and Cellular Biology.

[25]  Richard T. Lee,et al.  Focal Adhesion Kinase Signaling Regulates Cardiogenesis of Embryonic Stem Cells* , 2005, Journal of Biological Chemistry.

[26]  Eric F. Wieschaus,et al.  folded gastrulation, cell shape change and the control of myosin localization , 2005, Development.

[27]  V. Mironov,et al.  On the role of shear stress in cardiogenesis. , 2005, Endothelium : journal of endothelial cell research.

[28]  Qizhi Yao,et al.  Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell Line , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[29]  W. Marshall,et al.  De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia , 2005, PLoS biology.

[30]  T. Bartman,et al.  Mechanics and function in heart morphogenesis , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[31]  N. Hirokawa,et al.  FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination , 2005, Nature.

[32]  P. Janmey,et al.  Biomechanics and Mechanotransduction in Cells and Tissues Cell type-specific response to growth on soft materials , 2005 .

[33]  S. Rogers,et al.  DRhoGEF2 regulates actin organization and contractility in the Drosophila blastoderm embryo , 2005, Journal of Cell Biology.

[34]  C. Brokaw Computer simulation of flagellar movement IX. Oscillation and symmetry breaking in a model for short flagella and nodal cilia. , 2005, Cell motility and the cytoskeleton.

[35]  I. Kii,et al.  Inactivation of Rho/ROCK Signaling Is Crucial for the Nuclear Accumulation of FKHR and Myoblast Fusion* , 2004, Journal of Biological Chemistry.

[36]  Joyce Bischoff,et al.  Heart valve development: endothelial cell signaling and differentiation. , 2004, Circulation research.

[37]  Paul Martin,et al.  Parallels between tissue repair and embryo morphogenesis , 2004, Development.

[38]  D. Stainier,et al.  Early Myocardial Function Affects Endocardial Cushion Development in Zebrafish , 2004, PLoS biology.

[39]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[40]  L. Bonassar,et al.  Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces. , 2004, Archives of biochemistry and biophysics.

[41]  Eric P Hoffman,et al.  Embryonic myogenesis pathways in muscle regeneration , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[42]  Li Yuan,et al.  Flow regulates arterial-venous differentiation in the chick embryo yolk sac , 2003, Development.

[43]  F. Guilak,et al.  Mechanical signals as regulators of stem cell fate. , 2004, Current topics in developmental biology.

[44]  C. Marcelle,et al.  Intrinsic signals regulate the initial steps of myogenesis in vertebrates , 2003, Development.

[45]  M. Brueckner,et al.  Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse , 2003, Cell.

[46]  M. Pucéat,et al.  A dual role of the GTPase Rac in cardiac differentiation of stem cells. , 2003, Molecular biology of the cell.

[47]  P. Ratcliffe,et al.  Regulation of angiogenesis by hypoxia: role of the HIF system , 2003, Nature Medicine.

[48]  Melody A. Swartz,et al.  Interstitial Flow as a Guide for Lymphangiogenesis , 2003, Circulation research.

[49]  Ray Keller,et al.  How we are shaped: the biomechanics of gastrulation. , 2003, Differentiation; research in biological diversity.

[50]  G. Edwards,et al.  Forces for Morphogenesis Investigated with Laser Microsurgery and Quantitative Modeling , 2003, Science.

[51]  Jing Zhou,et al.  Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells , 2003, Nature Genetics.

[52]  Gabriel Acevedo-Bolton,et al.  Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis , 2003, Nature.

[53]  C. Tabin,et al.  A two-cilia model for vertebrate left-right axis specification. , 2003, Genes & development.

[54]  D. Ingber Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. , 2002, Circulation research.

[55]  A. Blangy,et al.  N-cadherin–dependent cell–cell contact regulates Rho GTPases and β-catenin localization in mouse C2C12 myoblasts , 2002, The Journal of cell biology.

[56]  Y. Saijoh,et al.  Determination of left–right patterning of the mouse embryo by artificial nodal flow , 2002, Nature.

[57]  E. Brandan,et al.  ECM is required for skeletal muscle differentiation independently of muscle regulatory factor expression. , 2002, American journal of physiology. Cell physiology.

[58]  H. Lehrach,et al.  Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left–right asymmetry , 2002, Nature Genetics.

[59]  Kenneth M. Yamada,et al.  Transmembrane crosstalk between the extracellular matrix and the cytoskeleton , 2001, Nature Reviews Molecular Cell Biology.

[60]  Michael I. Wilson,et al.  C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation , 2001, Cell.

[61]  J. Settleman Rac 'n Rho: the music that shapes a developing embryo. , 2001, Developmental cell.

[62]  B. Hinz,et al.  Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. , 2001, The American journal of pathology.

[63]  J. Lafitte,et al.  Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). , 2001, American journal of human genetics.

[64]  B. Geiger,et al.  Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk. , 2001, Nature reviews. Molecular cell biology.

[65]  Deepak Srivastava,et al.  A genetic blueprint for cardiac development , 2000, Nature.

[66]  Chu,et al.  Genetic analysis demonstrates a direct link between rho signaling and nonmuscle myosin function during drosophila morphogenesis , 2000, Genetics.

[67]  G. Garcı́a-Cardeña,et al.  Endothelial Dysfunction, Hemodynamic Forces, and Atherogenesis a , 2000, Annals of the New York Academy of Sciences.

[68]  Hayden Huang,et al.  Mechanotransduction and arterial smooth muscle cells: new insight into hypertension and atherosclerosis , 2000, Annals of medicine.

[69]  B. Olsen,et al.  Bone development. , 2000, Annual review of cell and developmental biology.

[70]  S. Amselem,et al.  Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. , 1999, American journal of human genetics.

[71]  N. Hirokawa,et al.  Randomization of Left–Right Asymmetry due to Loss of Nodal Cilia Generating Leftward Flow of Extraembryonic Fluid in Mice Lacking KIF3B Motor Protein , 1999, Cell.

[72]  S. Narumiya,et al.  Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. , 1999, Science.

[73]  S. Gordon,et al.  Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle. , 1999, American journal of physiology. Cell physiology.

[74]  M. Gimbrone Vascular Endothelium , Hemodynamic Forces , and Atherogenesis , 1999 .

[75]  C. McCulloch,et al.  The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts , 1999 .

[76]  C. McCulloch,et al.  The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. , 1999, The American journal of pathology.

[77]  P. Wigmore,et al.  The generation of fiber diversity during myogenesis. , 1998, The International journal of developmental biology.

[78]  Y. Wang,et al.  Cell locomotion and focal adhesions are regulated by substrate flexibility. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[79]  V. Ferrans,et al.  Nonmuscle myosin II-B is required for normal development of the mouse heart. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[80]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[81]  J. Tomasek,et al.  Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. , 1995, Experimental cell research.

[82]  E. Hunziker Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes , 1994, Microscopy research and technique.

[83]  F. Grinnell,et al.  Fibroblasts, myofibroblasts, and wound contraction , 1994, The Journal of cell biology.

[84]  D. Kiehart,et al.  Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. , 1993, Genes & development.

[85]  T. Akiyoshi,et al.  Epidermal ridge formation in the human fetus: a correlation to the appearance of basal cell heterogeneity and the expression of epidermal growth factor receptor and cytokeratin polypeptides in the epidermis. , 1991, The American journal of anatomy.

[86]  P. Benya,et al.  Microfilament modification by dihydrocytochalasin B causes retinoic acid-modulated chondrocytes to reexpress the differentiated collagen phenotype without a change in shape , 1988, The Journal of cell biology.

[87]  P. Benya,et al.  Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels , 1982, Cell.

[88]  Judah Folkman,et al.  Angiogenesis in vitro , 1980, Nature.

[89]  R. Reiter,et al.  Stage-related capacity for limb chondrogenesis in cell culture. , 1977, Developmental biology.

[90]  P. Camner,et al.  The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. , 1977, The New England journal of medicine.

[91]  R. Markwald,et al.  Structural development of endocardial cushions. , 1977, The American journal of anatomy.

[92]  D. Delain,et al.  Is fusion a trigger for myoblast differentiation? , 1975, Experimental cell research.

[93]  H. Green,et al.  Sublines of mouse 3T3 cells that accumulate lipid , 1974 .

[94]  C. Brokaw,et al.  Computer simulation of flagellar movement. I. Demonstration of stable bend propagation and bend initiation by the sliding filament model. , 1972, Biophysical journal.

[95]  R Umansky,et al.  The effect of cell population density on the developmental fate of reaggregating mouse limb bud mesenchyme. , 1966, Developmental biology.

[96]  P. Stucki,et al.  Bronchiectasis with situs inversus. , 1962, Archives of pediatrics.

[97]  A. R. Hale,et al.  Morphogenesis of volar skin in the human fetus. , 1952, The American journal of anatomy.

[98]  J. Holtfreter A study of the mechanics of gastrulation , 1944 .

[99]  J. F. Gudernatsch Concerning the mechanism and direction of embryonic foldings , 1913 .