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Tissue growth is the process by which a tissue increases its size. In animals, tissue growth occurs during embryonic development, post-natal growth, and tissue regeneration. The fundamental cellular basis for tissue growth is the process of cell proliferation, which involves both cell growth and cell division occurring in parallel. [1] [2] [3] [4]
How cell proliferation is controlled during tissue growth to determine final tissue size is an open question in biology. Uncontrolled tissue growth is a cause of cancer.
Differential rates of cell proliferation within an organ can influence proportions, as can the orientation of cell divisions, and thus tissue growth contributes to shaping tissues along with other mechanisms of tissue morphogenesis.
For some animal tissues, such as mammalian skin, it is clear that the growth of the skin is ultimately determined by the size of the body whose surface area the skin covers. This suggests that cell proliferation in skin stem cells within the basal layer is likely to be mechanically controlled to ensure that the skin covers the surface of the entire body. Growth of the body causes mechanical stretching of the skin, which is sensed by skin stem cells within the basal layer and consequently leads to both an increased rate of cell proliferation as well as promoting the planar orientation of stem cell divisions to produce new skin stem cells, rather than only producing differentiating supra-basal daughter cells.
Cell proliferation in skin stem cells within the basal layer can be driven by the mechanically-regulated YAP/TAZ family of transcriptional co-activators, which bind to TEAD-family DNA binding transcription factors in the nucleus to activate target gene expression and thereby drive cell proliferation.
For other animal tissues, such as the bones of the skeleton or the internal mammalian organs intestine, pancreas, kidney or brain, it remains unclear how developmental gene regulatory networks encoded in the genome lead to organs of such different sizes and proportions.
Although different animal tissues grow at different rates and produce organs of very different proportions, the overall growth rate of the entire animal body can be modulated by circulating hormones of the Insulin/IGF-1 family, which activate the PI3K/AKT/mTOR pathway in many cells of the body to increase the average rate of both cell growth and cell division, leading to increased cell proliferation rates in many tissues. In mammals, production of IGF-1 is induced by another circulating hormone called Growth Hormone. Excessive production of Growth Hormone or IGF-1 is responsible for giantism while insufficient production of these hormones is responsible for dwarfism.
Adult animal tissues such as skin or intestine maintain their size but undergo constant turnover of cells by proliferation of stem cells and progenitor cells while undergoing an equivalent loss of differentiated daughter cells via sloughing off. Gradients of Wnt signaling pathway activity appear to have a fundamental role in maintaining proliferation of stem and progenitor cells, at least in the intestine, and possibly also in skin.
Upon tissue damage, there is an upregulation in the activity of many pathways that control tissue growth, including the YAP/TAZ pathway, Wnt signaling pathway, and growth factors that activate the PI3K/AKT/mTOR pathway.
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.
A hormone is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required for the correct development of animals, plants and fungi. Due to the broad definition of a hormone, numerous kinds of molecules can be classified as hormones. Among the substances that can be considered hormones, are eicosanoids, steroids, amino acid derivatives, protein or peptides, and gases.
The meristem is a type of tissue found in plants. It consists of undifferentiated cells capable of cell division. Cells in the meristem can develop into all the other tissues and organs that occur in plants. These cells continue to divide until a time when they get differentiated and then lose the ability to divide.
A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word mamma, "breast". The mammary glands are arranged in organs such as the breasts in primates, the udder in ruminants, and the dugs of other animals. Lactorrhea, the occasional production of milk by the glands, can occur in any mammal, but in most mammals, lactation, the production of enough milk for nursing, occurs only in phenotypic females who have gestated in recent months or years. It is directed by hormonal guidance from sex steroids. In a few mammalian species, male lactation can occur. With humans, male lactation can occur only under specific circumstances.
Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis is greater than the overall rate of cellular degradation.
Cell proliferation is the process by which a cell grows and divides to produce two daughter cells. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation requires both cell growth and cell division to occur at the same time, such that the average size of cells remains constant in the population. Cell division can occur without cell growth, producing many progressively smaller cells, while cell growth can occur without cell division to produce a single larger cell. Thus, cell proliferation is not synonymous with either cell growth or cell division, despite the fact that these terms are sometimes used interchangeably.
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.
Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.
Myosatellite cells, also known as satellite cells, muscle stem cells or MuSCs, are small multipotent cells with very little cytoplasm found in mature muscle. Satellite cells are precursors to skeletal muscle cells, able to give rise to satellite cells or differentiated skeletal muscle cells. They have the potential to provide additional myonuclei to their parent muscle fiber, or return to a quiescent state. More specifically, upon activation, satellite cells can re-enter the cell cycle to proliferate and differentiate into myoblasts.
Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway, is a signaling pathway that controls organ size in animals through the regulation of cell proliferation and apoptosis. The pathway takes its name from one of its key signaling components—the protein kinase Hippo (Hpo). Mutations in this gene lead to tissue overgrowth, or a "hippopotamus"-like phenotype.
Tuberous sclerosis proteins 1 and 2, also known as TSC1 (hamartin) and TSC2 (tuberin), form a protein-complex. The encoding two genes are TSC1 and TSC2. The complex is known as a tumor suppressor. Mutations in these genes can cause tuberous sclerosis complex. Depending on the grade of the disease, intellectual disability, epilepsy and tumors of the skin, retina, heart, kidney and the central nervous system can be symptoms.
Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life.
Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.
Ovarian follicle activation can be defined as primordial follicles in the ovary moving from a quiescent (inactive) to a growing phase. The primordial follicle in the ovary is what makes up the “pool” of follicles that will be induced to enter growth and developmental changes that change them into pre-ovulatory follicles, ready to be released during ovulation. The process of development from a primordial follicle to a pre-ovulatory follicle is called folliculogenesis.
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.
Pierre Léopold is a research director at the French National Institute for Health and Medical Research (Inserm) and a member of the Institut de France. He heads the Unit of Genetics and Developmental Biology at the Curie Institute (Paris), and works with his team to understand the growth processes of organisms.