Morphogenesis

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Morphogenesis (from the Greek morphê shape and genesis creation, literally, "beginning of the shape") is the biological process that causes an organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of cell growth and cellular differentiation.

The process controls the organized spatial distribution of cells during the embryonic development of an organism. Morphogenesis can take place also in a mature organism, in cell culture or inside tumor cell masses. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle, or describes the evolution of a body structure within a taxonomic group.

Morphogenetic responses may be induced in organisms by hormones, by environmental chemicals ranging from substances produced by other organisms to toxic chemicals or radionuclides released as pollutants, and other plants, or by mechanical stresses induced by spatial patterning of the cells.

History[edit]

Some of the earliest ideas and mathematical descriptions on how physical processes and constraints affect biological growth, and hence natural patterns such as the spirals of phyllotaxis, were written by D'Arcy Wentworth Thompson (1917)[1][2][a] and Alan Turing (1952).[3] Where Thompson explained animal body shapes as being created by varying rates of growth in different directions, for instance to create the spiral shell of a snail, Turing correctly predicted the diffusion of two different chemical signals, one activating and one deactivating growth, to set up patterns of development. The fuller understanding of the mechanisms involved in actual organisms required the discovery of DNA and the development of molecular biology and biochemistry.

The term histomorphogenesis was coined by Ricqlès et al. (2001) for the same process in bone histology.[4]

Molecular basis[edit]

Several types of molecules are particularly important during morphogenesis. Morphogens are soluble molecules that can diffuse and carry signals that control cell differentiation decisions in a concentration-dependent fashion. Morphogens typically act through binding to specific protein receptors. An important class of molecules involved in morphogenesis are transcription factor proteins that determine the fate of cells by interacting with DNA. These can be coded for by master regulatory genes and either activate or deactivate the transcription of other genes; in turn, these secondary gene products can regulate the expression of still other genes in a regulatory cascade. At the end of this cascade, another class of molecules involved in morphogenesis are molecules that control cellular behaviors (for example cell migration) or, more generally, their properties, such as cell adhesion or cell contractility. For example, during gastrulation, clumps of stem cells switch off their cell-to-cell adhesion, become migratory, and take up new positions within an embryo where they again activate specific cell adhesion proteins and form new tissues and organs. A number of developmental signaling pathways have been implicated in morphogenesis, including Wnt, Hedgehog, and ephrins.[5] Several examples that illustrate the roles of morphogens, transcription factors and cell adhesion molecules in morphogenesis are discussed below.

Cellular basis[edit]

Example of cell sorting out with cultured P19 embryonal carcinoma cells. Live cells were stained with either DiI (red) or DiO (green). The red cells were genetically altered and express higher levels of E-cadherin than the green cells. After labeling, the two populations of cells were mixed and cultured together allowing the cells to form large multi-cellular mixed aggregates. Individual cells are less than 10 micrometres in diameter. The image was captured by scanning confocal microscopy.

Morphogenesis arises because of changes in the cellular structure or how cells interact in tissues.[6] These changes can result in tissue elongation, thinning, folding or separation of one tissue into distinct layers. The latter case is often referred as cell sorting. Cell "sorting out" consists of cells moving so as to sort into clusters that maximize contact between cells of the same type. The ability of cells to do this has been proposed to arise from differential cell adhesion by Malcolm Steinberg through his Differential Adhesion Hypothesis. Tissue separation can also occur via more dramatic cellular differentiation events during which epithelial cells become mesenchymal (see Epithelial-mesenchymal transition). Mesechymal cells typically leave the epithelial tissue as a consequence of changes in cell adhesive and contractile properties. Following epithelial-mesenchymal transition, cells can migrate away from an epithelium and then associate with other similar cells in a new location.

Cell-cell adhesion[edit]

During embryonic development, cells are restricted to different layers due to differential affinities. One of the ways this can occur is when cells share the same cell-to-cell adhesion molecules. For instance, homotypic cell adhesion can maintain boundaries between groups of cells that have different adhesion molecules. Furthermore, cells can sort based upon differences in adhesion between the cells, so even two populations of cells with different levels of the same adhesion molecule can sort out. In cell culture cells that have the strongest adhesion move to the center of a mixed aggregates of cells. Moreover, cell-cell adhesion is often modulated by cell contractility, which can exert forces on the cell-cell contacts so that two cell populations with equal levels of the same adhesion molecule can sort out.

The molecules responsible for adhesion are called cell adhesion molecules (CAMs). Several types of cell adhesion molecules are known and one major class of these molecules are cadherins. There are dozens of different cadherins that are expressed on different cell types. Cadherins bind to other cadherins in a like-to-like manner: E-cadherin (found on many epithelial cells) binds preferentially to other E-cadherin molecules. Mesenchymal cells usually express other cadherin types such as N-cadherin.

Extracellular matrix[edit]

The extracellular matrix (ECM) is involved in keeping tissues separated, providing structural support or providing a structure for cells to migrate on. Collagen, laminin, and fibronectin are major ECM molecules that are secreted and assembled into sheets, fibers, and gels. Multisubunit transmembrane receptors called integrins are used to bind to the ECM. Integrins bind extracellularly to fibronectin, laminin, or other ECM components, and intracellularly to microfilament-binding proteins α-actinin and talin to link the cytoskeleton with the outside. Integrins also serve as receptors to trigger signal transduction cascades when binding to the ECM. A well-studied example of morphogenesis that involves ECM is mammary gland ductal branching.[7][8]

Cell contractility[edit]

Tissues can change their shape and separate into distinct layers via cell contractility. Just like in muscle cells, myosin can contract different parts of the tissue to change its shape or structure. Typical examples of myosin-driven contractility in tissue morphogenesis occur during the separation of Caenorhabditis elegans, drosophila and zebrafish germ layers. Often, during embryonic morphogenesis, cell contractility occurs via periodic pulses of contraction.

See also[edit]

Notes[edit]

a. ^ Thompson's book is often cited. An abridged version, comprising 349 pages, remains in print and readily obtainable.[9] An unabridged version, comprising 1116 pages, has also been published.[10]

References[edit]

  1. ^ Thompson, D'Arcy Wentworth (1917), On Growth and Form, Cambridge University Press, retrieved 12 December 2012  Full text at archive.org 
  2. ^ Montell, Denise J (5 December 2008), "Morphogenetic Cell Movements: Diversity from Modular Mechanical Properties", Science 322: 1502–1505, Bibcode:2008Sci...322.1502M, doi:10.1126/science.1164073, retrieved 11 December 2012 
  3. ^ Turing, A. M. (1952). "The Chemical Basis of Morphogenesis". Philosophical Transactions of the Royal Society B 237 (641): 37–72. Bibcode:1952RSPTB.237...37T. doi:10.1098/rstb.1952.0012. 
  4. ^ Ricqles, A. de; Mateus, O.; Antunes, M. Telles ; & Taquet, P. (2001). "Histomorphogenesis of embryos of Upper Jurassic Theropods from Lourinhã (Portugal)". Comptes rendus de l'Académie des sciences - Série IIa - Sciences de la Terre et des planètes 332 (10): 647–656. Bibcode:2001CRASE.332..647D. doi:10.1016/S1251-8050(01)01580-4. 
  5. ^ Kouros-Mehr, H; Werb Z (2006). "Candidate regulators of mammary branching morphogenesis identified by genome-wide transcript analysis.". Dev Dyn. 235 (12): 3404–12. doi:10.1002/dvdy.20978. PMID 17039550. 
  6. ^ Gilbert, Scott F. (2000). "Morphogenesis and Cell Adhesion". Developmental biology (6th ed.). Sunderland, Mass: Sinauer Associates. ISBN 0-87893-243-7. 
  7. ^ Fata JE, Werb Z, Bissell MJ (2004). "Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes". Breast Cancer Res. 6 (1): 1–11. doi:10.1186/bcr634. PMC 314442. PMID 14680479. 
  8. ^ Sternlicht MD (2006). "Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis". Breast Cancer Res. 8 (1): 201. doi:10.1186/bcr1368. PMC 1413974. PMID 16524451. 
  9. ^ Thompson, D'Arcy; John Tyler Bonner (editor) (2004 printing. Abridged ed. 1961 (first published 1917)), On Growth and Form, Cambridge, U.K., & New York: Cambridge University Press, ISBN 0-521-43776-8, retrieved 11 December 2012   
  10. ^ Thompson, D'Arcy Wentworth (1992), On Growth and Form: The Complete Revised Edition, New York: Dover, ISBN 0-486-67135-6 

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