Hertwig rule

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Hertwig's rule, or the long axis rule states that a cell divides along its long axis. Introduced by the German zoologist Oscar Hertwig in 1884, the rule emphasizes the cell shape as a default mechanism of spindle apparatus orientation. Hertwig's rule predicts cell division orientation, which is important for tissue architecture, cell fate and morphogenesis.

Contents

Discovery

Hertwig's experiments studied the orientation of frog egg divisions. The frog egg has a round shape and the first division occurs in a random orientation. Hertwig compressed the egg between two parallel plates. The compression forced the egg to change its shape from round to elongated. Hertwig noticed that elongated egg divides not randomly, but orthogonally to its long axis. The new daughter cells were formed along the longest axis of the cell. This observation thus became known as 'Hertwig's rule' or 'long axis rule'. [1]

Confirmation and mechanism

Cartoon of the dividing epithelium cell surrounded by epithelium tissue. Spindle apparatus rotates inside the cell. The rotation is a result of astral microtubules pulling towards tri-cellular-junctions (TCJ), signaling centers localized at the regions where three cells meet. TCJ orients spindle apparatus during cell division.png
Cartoon of the dividing epithelium cell surrounded by epithelium tissue. Spindle apparatus rotates inside the cell. The rotation is a result of astral microtubules pulling towards tri-cellular-junctions (TCJ), signaling centers localized at the regions where three cells meet.

Recent studies in animal and plant systems support the 'long axis rule'. The studied systems include the mouse embryo, [2] Drosophila epithelium, [3] Xenopus blastomeres (Strauss 2006), MDCK cell monolayers [4] and plants (Gibson et al., 2011). The mechanism of the 'long axis rule' relies on interphase cell long axis sensing. However, during division many animal cell types undergo cell rounding, causing the long axis to disappear as the cell becomes round. It is at this rounding stage that the decision on the orientation of the cell division is made by the spindle apparatus. The spindle apparatus rotates in the round cell and after several minutes the spindle position is stabilised preferentially along the interphase cell long axis. The cell then divides along the spindle apparatus orientation. The first insights into how cells could remember their long axis came from studies on the Drosophila epithelium. The study indicated the participation of tricellular junctions (TCJs) in determining the spindle orientation. TCJs localized at the regions where three or more cells meet. As cells round up during mitosis, TCJs serve as spatial landmarks. The orientation of TCJs remains stable, independent of the shape changes associated with cell rounding. The positions of TCJs encode information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. [3] However this study is limited to only one type of epithelia in Drosophila melanogaster and has not been shown to be true in other epithelial types.

Mechanobiology

It has been shown that mechanical force can cause cells to divide against their long axis and instead with the direction of mechanical stretch in MDCK monolayers. [5]

Importance

Cell divisions along 'long axis' are proposed to be implicated in the morphogenesis, tissue response to stresses and tissue architecture. Division along the long cell axis reduces global tissue stress more rapidly than random divisions or divisions along the axis of mechanical stress. Long-axis division contributes to the formation of isotropic cell shapes within the monolayer.

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Type of cell division in sexually-reproducing organisms used to produce gametes

Meiosis is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote.

Morphogenesis is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation.

<span class="mw-page-title-main">Mitosis</span> Process in which replicated chromosomes are separated into two new identical nuclei

In cell biology, mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintained. Therefore, mitosis is also known as equational division. In general, mitosis is preceded by S phase of interphase and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Cell division</span> Process by which living cells divide

Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. In cell biology, mitosis (/maɪˈtoʊsɪs/) is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis all together define the mitotic (M) phase of animal cell cycle—the division of the mother cell into two genetically identical daughter cells. Meiosis results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

<span class="mw-page-title-main">Cytokinesis</span> Part of the cell division process

Cytokinesis is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division. The MTOC is a major site of microtubule nucleation and can be visualized in cells by immunohistochemical detection of γ-tubulin. The morphological characteristics of MTOCs vary between the different phyla and kingdoms. In animals, the two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation.

Cell junctions or junctional complexes, are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.

In embryology, cleavage is the division of cells in the early development of the embryo, following fertilization. The zygotes of many species undergo rapid cell cycles with no significant overall growth, producing a cluster of cells the same size as the original zygote. The different cells derived from cleavage are called blastomeres and form a compact mass called the morula. Cleavage ends with the formation of the blastula, or of the blastocyst in mammals.

Endoreduplication is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity. Examples of endoreplication characterized in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions. While endoreplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues.

In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.

<span class="mw-page-title-main">Planar cell polarity</span>

Planar Cell Polarity (PCP) is the protein mediated signaling that coordinates the orientation of cells in a layer of epithelial tissue. In vertebrates, examples of mature PCP oriented tissue are the stereo-cilia bundles in the inner ear, motile cilia of the epithelium, and cell motility in epidermal wound healing. Additionally, PCP is known to be crucial to major developmental time points including coordinating convergent extension during gastrulation and coordinating cell behavior for neural tube closure. Cells orient themselves and their neighbors by establishing asymmetric expression of PCP components on opposing cell members within cells to establish and maintain the directionality of the cells. Some of these PCP components are transmembrane proteins which can proliferate the orientation signal to the surrounding cells.

<span class="mw-page-title-main">Germ-band extension</span>

Germ-band extension is a morphological process widely studied in Drosophila melanogaster in which the germ-band, which develops into the segmented trunk of the embryo, approximately doubles in length along the anterior-posterior axis while subsequently narrowing along the dorsal-ventral axis.

Amitosis, also called karyostenosis or direct cell division or binary fission, is cell proliferation that does not occur by mitosis, the mechanism usually identified as essential for cell division in eukaryotes. The polyploid macronucleus found in ciliates divides amitotically. While normal mitosis results in a precise division of parental alleles, amitosis results in a random distribution of parental alleles. Ploidy levels of >1000 in some species means both parental alleles can be maintained over many generations, while species with fewer numbers of each chromosome will tend to become homozygous for one or the other parental allele through a process known as phenotypic or allelic assortment.

Mitotic cell rounding is a shape change that occurs in most animal cells that undergo mitosis. Cells abandon the spread or elongated shape characteristic of interphase and contract into a spherical morphology during mitosis. The phenomenon is seen both in artificial cultures in vitro and naturally forming tissue in vivo.

Cell division orientation is the direction along which the new daughter cells are formed. Cell division orientation is important for morphogenesis, cell fate and tissue homeostasis. Abnormalities in the cell division orientation leads to the malformations during development and cancerous tissues. Factors that influence cell division orientation are cell shape, anisotropic localization of specific proteins and mechanical tensions.

<span class="mw-page-title-main">Madin-Darby canine kidney cells</span> Cell line

Madin-Darby canine kidney (MDCK) cells are a model mammalian cell line used in biomedical research. MDCK cells are used for a wide variety of cell biology studies including cell polarity, cell-cell adhesions, collective cell motility, toxicity studies, as well as responses to growth factors. It is one of few cell culture models that is suited for 3D cell culture and multicellular rearrangements known as branching morphogenesis.

Barry James Thompson is an Australian and British developmental biologist and cancer biologist. He is a professor of the John Curtin School of Medical Research at the Australian National University in Canberra. Thompson is known for identifying genes, proteins and mechanisms involved in epithelial polarity, morphogenesis and cell signaling via the Wnt and Hippo signaling pathways, which have key roles in human cancer.

This glossary of cell biology is a list of definitions of terms and concepts commonly used in the study of cell biology and related disciplines in biology, including developmental biology, genetics, microbiology, molecular biology, and biochemistry.

References

  1. Hertwig O (1884). "Das Problem der Befruchtung und der Isotropie des Eies. Eine Theorie der Vererbung". Jenaische Zeitschrift für Naturwissenschaft. 18: 274.
  2. Gray D, Plusa B, Piotrowska K, Ha J, Glower D, Zernicka-Goetz M (2004). "First cleavage of the mouse embryo responds to change in egg shape at fertilization". Current Biology. 14 (5): 397–405. doi: 10.1016/j.cub.2004.02.031 . PMID   15028215.
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  4. Wyatt T, Harris A, Lam M, Cheng Q, Bellis J, Dimitracopoulos A, Kabla A, Charras G, Baumm B (2015). "Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis". Proceedings of the National Academy of Sciences. 112 (18): 5726–5731. Bibcode:2015PNAS..112.5726W. doi: 10.1073/pnas.1420585112 . PMC   4426437 . PMID   25908119.
  5. Hart, Kevin C.; Tan, Jiongyi; Siemers, Kathleen A.; Sim, Joo Yong; Pruitt, Beth L.; Nelson, W. James; Gloerich, Martijn (18 July 2017). "E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape". Proceedings of the National Academy of Sciences. 114 (29): E5845–E5853. doi: 10.1073/pnas.1701703114 . PMC   5530667 . PMID   28674014.