Cell division orientation

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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, [1] [2] [3] anisotropic localization of specific proteins and mechanical tensions. [4]

Contents

Implication for morphogenesis

Cell division orientation is one of the mechanisms that shapes tissue during development and morphogenesis. Along with cell shape changes, cell rearrangements, apoptosis and growth, oriented cell division modifies the geometry and topology of live tissue in order to create new organs and shape the organisms. Reproducible patterns of oriented cell divisions were described during morphogenesis of Drosophila embryos, Arabidopsis thaliana embryos, [5] Drosophila pupa, [6] zebrafish embryos [7] and mouse early embryos. Oriented cell divisions contribute to the tissue elongation and the release of mechanical stress. While in the first case oriented cell division acts as active contributor to the morphogenesis, the latter case is a passive response to the external mechanical tensions. [8]

Implication for tissue homeostasis

In several tissues, such as columnar epithelium, the cells divide along the plane of the epithelium. Such divisions insert new formed cells in the epithelium layer. The disregulation of the orientation of cell divisions result in the creation of the cell out of epithelium and is observed at the initial stages of cancer.

Regulation

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.

More than a century ago Oskar Hertwig proposed that the cell division orientation is determined by the shape of the cell (1884), known as Hertwig rule. [9] In the epithelium the cells 'reads' its shape through the specific cell junction called tricellular junctions (TCJ). TCJ provide mechanical and geometrical clues for the spindle apparatus to ensure that cell divide along its long axis. [10] Several factors could regulate cell shape and therefore orientation of cell division. Among these factors is the anisotropic mechanical stress. This stress could be the result of the external mechanical deformation of generated intracellularly by non-isotropic localization of specific proteins.

Related Research Articles

Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem cells in the adult organism.

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.

Spindle apparatus Array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart

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.

Ectoderm

The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm and endoderm. It emerges and originates from the outer layer of germ cells. The word ectoderm comes from the Greek ektos meaning "outside", and derma meaning "skin".

Gravitropism

Gravitropism is a coordinated process of differential growth by a plant in response to gravity pulling on it. It also occurs in fungi. Gravity can be either "artificial gravity" or natural gravity. It is a general feature of all higher and many lower plants as well as other organisms. Charles Darwin was one of the first to scientifically document that roots show positive gravitropism and stems show negative gravitropism. That is, roots grow in the direction of gravitational pull and stems grow in the opposite direction. This behavior can be easily demonstrated with any potted plant. When laid onto its side, the growing parts of the stem begin to display negative gravitropism, growing upwards. Herbaceous (non-woody) stems are capable of a degree of actual bending, but most of the redirected movement occurs as a consequence of root or stem growth outside. The mechanism is based on the Cholodny–Went model which was proposed in 1927, and has since been modified. Although the model has been criticized and continues to be refined, it has largely stood the test of time.

Cell junctions 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.

Enamel organ

The enamel organ, also known as the dental organ, is a cellular aggregation seen in a developing tooth and it lies above the dental papilla. The enamel organ is responsible for the formation of enamel, initiation of dentine formation, establishment of the shape of a tooth's crown, and establishment of the dentoenamel junction.

A cementoblast is a biological cell that forms from the follicular cells around the root of a tooth, and whose biological function is cementogenesis, which is the formation of cementum. The mechanism of differentiation of the cementoblasts is controversial but circumstantial evidence suggests that an epithelium or epithelial component may cause dental sac cells to differentiate into cementoblasts, characterised by an increase in length. Other theories involve Hertwig epithelial root sheath (HERS) being involved.

Mesenchyme Type of connective tissue found mostly during the embryonic development of bilateral triploblast animals

Mesenchyme is a type of loosely organised animal embryonic connective tissue of undifferentiated cells that gives rise to blood and lymph vessels, bone, and muscle.

Eye development Formation of the eye during embryonic development

Eye formation in the human embryo begins at approximately three weeks into embryonic development and continues through the tenth week. Cells from both the mesodermal and the ectodermal tissues contribute to the formation of the eye. Specifically, the eye is derived from the neuroepithelium, surface ectoderm, and the extracellular mesenchyme which consists of both the neural crest and mesoderm.

Within the field of developmental biology, one goal is to understand how a particular cell develops into a final cell type, known as fate determination. Within an embryo, several processes play out at the cellular and tissue level to create an organism. These processes include cell proliferation, differentiation, cellular movement and programmed cell death. Each cell in an embryo receives molecular signals from neighboring cells in the form of proteins, RNAs and even surface interactions. Almost all animals undergo a similar sequence of events during very early development, a conserved process known as embryogenesis. During embryogenesis, cells exist in three germ layers, and undergo gastrulation. While embryogenesis has been studied for more than a century, it was only recently that scientists discovered that a basic set of the same proteins and mRNAs are involved in embryogenesis. Evolutionary conservation is one of the reasons that model systems such as the fly, the mouse, and other organisms are used as models to study embryogenesis and developmental biology. Studying model organisms provides information relevant to other animals, including humans. While studying the different model systems, cells fate was discovered to be determined via multiple ways, two of which are by the combination of transcription factors the cells have and by the cell-cell interaction. Cells’ fate determination mechanisms were categorized into three different types, autonomously specified cells, conditionally specified cells, or syncytial specified cells. Furthermore, the cells’ fate was determined mainly using two types of experiments, cell ablation and transplantation. The results obtained from these experiments, helped in identifying the fate of the examined cells.

FGF7

Keratinocyte growth factor is a protein that in humans is encoded by the FGF7 gene.

Cytoneme

Cytonemes are thin, cellular projections that are specialized for exchange of signaling proteins between cells. Cytonemes emanate from cells that make signaling proteins, extending directly to cells that receive signaling proteins. Cytonemes also extend directly from cells that receive signaling proteins to cells that make them.

Cell polarity

Cell polarity refers to spatial differences in shape, structure, and function within a cell. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity, neurons in which signals propagate in one direction from dendrites to axons, and migrating cells. Furthermore, cell polarity is important during many types of asymmetric cell division to set up functional asymmetries between daughter cells.

Symmetry breaking in biology is the process by which uniformity is broken, or the number of points to view invariance are reduced, to generate a more structured and improbable state. That is to say, symmetry breaking is the event where symmetry along a particular axis is lost to establish a polarity. Polarity is a measure for a biological system to distinguish poles along an axis. This measure is important because it is the first step to building complexity. For example, during organismal development, one of the first steps for the embryo is to distinguish its dorsal-ventral axis. The symmetry-breaking event that occurs here will determine which end of this axis will be the ventral side, and which end will be the dorsal side. Once this distinction is made, then all the structures that are located along this axis can develop at the proper location. As an example, during human development, the embryo needs to establish where is ‘back’ and where is ‘front’ before complex structures, such as the spine and lungs, can develop in the right location. This relationship between symmetry breaking and complexity was articulated by P.W. Anderson. He speculated that increasing levels of broken symmetry in many-body systems correlates with increasing complexity and functional specialization. In a biological perspective, the more complex an organism is, the higher number of symmetry-breaking events can be found. Without symmetry breaking, building complexity in organisms would be very difficult.

FOXJ1

Forkhead box protein J1 is a protein that in humans is encoded by the FOXJ1 gene. It is a member of the Forkhead/winged helix (FOX) family of transcription factors that is involved in ciliogenesis. FOXJ1 is expressed in ciliated cells of the lung, choroid plexus, reproductive tract, embryonic kidney and pre-somite embryo stage.

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 phenomena is seen both in artificial cultures in vitro and naturally forming tissue in vivo.

Hertwig's rule or 'long axis rule' states that a cell divides along its long axis. It was introduced by german zoologist Oscar Hertwig in 1884. The rule emphasizes the cell shape to be a default mechanism of spindle apparatus orientation. Hertwig's rule predicts cell division orientation, that is important for tissue architecture, cell fate and morphogenesis.

Madin-Darby canine kidney cells 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, 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.

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