Morphogenesis

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, unified in evolutionary developmental biology (evo-devo).

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

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 in his 1917 book On Growth and Form[1][2][a] and Alan Turing in his The Chemical Basis of Morphogenesis (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 a mechanism of morphogenesis, the diffusion of two different chemical signals, one activating and one deactivating growth, to set up patterns of development, decades before the formation of such patterns was observed.[4] The fuller understanding of the mechanisms involved in actual organisms required the discovery of the structure of DNA in 1953, and the development of molecular biology and biochemistry.

Genetic and molecular basis

Morphogenesis is controlled by a "toolkit" of genes which switch development on and off at precise times and places. Here, gap genes in the fruit fly are switched on by genes such as bicoid, setting up stripes which create the body's segmental form.

Several types of molecules are important in morphogenesis. Morphogens are soluble molecules that can diffuse and carry signals that control cell differentiation via concentration gradients. 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 of gene regulatory networks. At the end of this cascade are classes of molecules that control cellular behaviors such as 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. Developmental signaling pathways implicated in morphogenesis include Wnt, Hedgehog, and ephrins.[5]

Cellular basis

Cell sorting out with cultured P19 embryonal carcinoma cells. Live cells were stained with DiI (red) or DiO (green). The red cells were genetically altered and express higher levels of E-cadherin than the green cells. The mixed culture forms large multi-cellular aggregates.

At a tissue level, ignoring the means of control, morphogenesis arises because of cellular proliferation and motility.[6] Morphogenesis also involves changes in the cellular structure or how cells interact in tissues. These changes can result in tissue elongation, thinning, folding, invasion 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). Mesenchymal 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.[7]

Cell-cell adhesion

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.[8][9]

Extracellular matrix

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.[10][11]

Cell contractility

Tissues can change their shape and separate into distinct layers via cell contractility. Just as in muscle cells, myosin can contract different parts of the cytoplasm to change its shape or structure. Myosin-driven contractility in embryonic tissue morphogenesis is seen during the separation of germ layers in the model organisms Caenorhabditis elegans, Drosophila and zebrafish. There are often periodic pulses of contraction in embryonic morphogenesis. A model called the cell state splitter involves alternating cell contraction and expansion, initiated by a bistable organelle at the apical end of each cell. The organelle consists of microtubules and microfilaments in mechanical opposition. It responds to local mechanical perturbations caused by morphogenetic movements. These then trigger traveling waves of contraction or expansion over presumptive tissues that determine cell type and is followed by cell differentiation. The cell state splitter was first proposed to explain neural plate morphogenesis during gastrulation of the axolotl[12] and the model was later generalized to all of morphogenesis.[13][14]

See also

Notes

a. ^ Thompson's book is often cited. An abridged version, comprising 349 pages, remains in print and readily obtainable.[15] An unabridged version, comprising 1116 pages, has also been published.[16]

References

  1. ↑ Thompson, D'Arcy Wentworth (1917). On Growth and Form. Cambridge University Press.
  2. ↑ Montell, Denise J (5 December 2008), "Morphogenetic Cell Movements: Diversity from Modular Mechanical Properties" (PDF), Science, 322: 1502–1505, Bibcode:2008Sci...322.1502M, PMID 19056976, doi:10.1126/science.1164073
  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. ↑ Hiscock, Tom W.; Megason, Sean G. (2015). "Orientation of Turing-like Patterns by Morphogen Gradients and Tissue Anisotropies". Cell Systems. 1 (6): 408–416. doi:10.1016/j.cels.2015.12.001.
  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. PMC 2730892 Freely accessible. PMID 17039550. doi:10.1002/dvdy.20978.
  6. ↑ Montévil, Maël; Speroni, Lucia; Sonnenschein, Carlos; Soto, Ana M. (2016). "Modeling mammary organogenesis from biological first principles: Cells and their physical constraints". Progress in Biophysics and Molecular Biology. From the Century of the Genome to the Century of the Organism: New Theoretical Approaches. 122 (1): 58–69. PMID 27544910. doi:10.1016/j.pbiomolbio.2016.08.004.
  7. ↑ Gilbert, Scott F. (2000). "Morphogenesis and Cell Adhesion". Developmental biology (6th ed.). Sunderland, Mass: Sinauer Associates. ISBN 0-87893-243-7.
  8. ↑ Hulpiau, P.; van Roy, F. (February 2009). "Molecular evolution of the cadherin superfamily". Int. J. Biochem. Cell Biol. 41 (2): 349–69. PMID 18848899. doi:10.1016/j.biocel.2008.09.027.
  9. ↑ Angst, B.; Marcozzi, C.; Magee, A. (February 2001). "The cadherin superfamily: diversity in form and function". J Cell Sci. 114 (Pt 4): 629–41. PMID 11171368.
  10. ↑ 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. PMC 314442 Freely accessible. PMID 14680479. doi:10.1186/bcr634.
  11. ↑ Sternlicht MD (2006). "Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis". Breast Cancer Res. 8 (1): 201. PMC 1413974 Freely accessible. PMID 16524451. doi:10.1186/bcr1368.
  12. ↑ Gordon R, Brodland GW. The cytoskeletal mechanics of brain morphogenesis. Cell state splitters cause primary neural induction. Cell Biophys. 1987 Dec;11:177-238.
  13. ↑ Gordon, NK,Gordon,R. The organelle of differentiation in embryos: the cell state splitter Theoretical Biology and Medical Modelling, 13(11) 2016
  14. ↑ Gordon NK, Gordon R Embryogenesis explained World Scientific Nov 2016, ISBN 978-981-4350-48-8
  15. ↑ Thompson, D'Arcy; John Tyler Bonner (editor) (2004) [1917, abridged 1961], On Growth and Form, Cambridge, U.K., & New York: Cambridge University Press, ISBN 0-521-43776-8, retrieved 11 December 2012  
  16. ↑ Thompson, D'Arcy Wentworth (1992), On Growth and Form: The Complete Revised Edition, New York: Dover, ISBN 0-486-67135-6

Further reading

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.