Regeneration (biology)
Regeneration in biology is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which the necrotic tissue becomes fibrotic.
At its most elementary level, regeneration is mediated by the molecular processes of gene regulation and involves the cellular processes of cell proliferation, morphogenesis and cell differentiation. Regeneration in biology, however, mainly refers to the morphogenic processes that characterize the phenotypic plasticity of traits allowing multi-cellular organisms to repair and maintain the integrity of their physiological and morphological states. Above the genetic level, regeneration is fundamentally regulated by asexual cellular processes. Regeneration is different from reproduction. For example, hydra perform regeneration but reproduce by the method of budding.
The regenerative process occurs in two multi-step phases: the preparation phase and the redevelopment phase. Regeneration begins with an amputation which triggers the first phase. Right after the amputation, migrating epidermal cells form a wound epithelium which thickens, through cell division, throughout the first phase to form a cap around the site of the wound. The cells underneath this cap then begin to rapidly divide and form a cone shaped end to the amputation known as a blastema. Included in the blastema are skin, muscle, and cartilage cells that de-differentiate and become similar to stem cells in that they can become multiple types of cells. Cells differentiate to the same purpose they originally filled meaning skin cells again become skin cells and muscle cells become muscles. These de-differentiated cells divide until enough cells are available at which point they differentiate again and the shape of the blastema begins to flatten out. It is at this point that the second phase begins, the redevelopment of the limb. In this stage, genes signal to the cells to differentiate themselves and the various parts of the limb are developed. The end result is a limb that looks and operates identically to the one that was lost, usually without any visual indication that the limb is newly generated.
The hydra and the planarian flatworm have long served as model organisms for their highly adaptive regenerative capabilities. Once wounded, their cells become activated and restore the organs back to their pre-existing state. The Caudata, an order of tailed amphibians, is possibly the most adept vertebrate group at regeneration, given their capability of regenerating limbs, tails, jaws, eyes and a variety of internal structures. The regeneration of organs is a common and widespread adaptive capability among metazoan creatures. In a related context, some animals are able to reproduce asexually through fragmentation, budding, or fission. A planarian parent, for example, will constrict, split in the middle, and each half generates a new end to form two clones of the original.
Echinoderms, crayfish, many reptiles, and amphibians exhibit remarkable examples of tissue regeneration. The case of autotomy, for example, serves as a defensive function as the animal detaches a limb or tail to avoid capture. After the limb or tail has been autotomized, cells move into action and the tissues will regenerate. In some cases a shed limb can itself regenerate a new individual. Limited regeneration of limbs occurs in most fishes and salamanders, and tail regeneration takes place in larval frogs and toads. The whole limb of a salamander or a triton will grow repeatedly after amputation. In reptiles, chelonians, crocodilians and snakes are unable to regenerate lost parts, but many kinds of lizards, geckos and iguanas possess regeneration capacity in a high degree. Usually, it involves dropping a section of their tail and regenerating it as part of a defense mechanism. While escaping a predator, if the predator catches the tail, it will disconnect.
Ecosystems
Ecosystems can be regenerative. Following a disturbance, such as a fire or pest outbreak in a forest, pioneering species will occupy, compete for space, and establish themselves in the newly opened habitat. The new growth of seedlings and community assembly process is known as regeneration in ecology.Cellular molecular fundamentals
Pattern formation in the morphogenesis of an animal is regulated by genetic induction factors that put cells to work after damage has occurred. Neural cells, for example, express growth-associated proteins, such as GAP-43, tubulin, actin, an array of novel neuropeptides, and cytokines that induce a cellular physiological response to regenerate from the damage. Many of the genes that are involved in the original development of tissues are reinitialized during the regenerative process. Cells in the primordia of zebrafish fins, for example, express four genes from the homeobox msx family during development and regeneration.Tissues
"Strategies include the rearrangement of pre-existing tissue, the use of adult somatic stem cells and the dedifferentiation and/or transdifferentiation of cells, and more than one mode can operate in different tissues of the same animal. All these strategies result in the re-establishment of appropriate tissue polarity, structure and form." During the developmental process, genes are activated that serve to modify the properties of cell as they differentiate into different tissues. Development and regeneration involves the coordination and organization of populations cells into a blastema, which is "a mound of stem cells from which regeneration begins". Dedifferentiation of cells means that they lose their tissue-specific characteristics as tissues remodel during the regeneration process. This should not be confused with the transdifferentiation of cells which is when they lose their tissue-specific characteristics during the regeneration process, and then re-differentiate to a different kind of cell.In animals
Arthropods
Limb regeneration
Many arthropods can regenerate limbs and other appendages following either injury or autotomy. Regeneration capacity is constrained by the developmental stage and ability to molt.Crustaceans, which continually molt, can regenerate throughout their lifetimes. While molting cycles are generally hormonally regulated, limb amputation induces premature molting.
Hemimetabolous insects such as crickets can regenerate limbs as nymphs, before their final molt.
Holometabolous insects can regenerate appendages as larvae prior to the final molt and metamorphosis. Beetle larvae, for example, can regenerate amputated limbs. Fruit fly larvae do not have limbs but can regenerate their appendage primordia, imaginal discs. In both systems, the regrowth of the new tissue delays pupation.
Mechanisms underlying appendage limb regeneration in insects and crustaceans are highly conserved. During limb regeneration species in both taxa form a blastema that proliferates and grows to repattern the missing tissue.
Venom regeneration
s, including scorpions, are known to regenerate their venom, although the content of the regenerated venom is different from the original venom during its regeneration, as the venom volume is replaced before the active proteins are all replenished.Fruit fly model
The fruit fly Drosophila melanogaster is a useful model organism to understand the molecular mechanisms that control regeneration, especially gut and germline regeneration. In these tissues, resident stem cells continually renew lost cells. The Hippo signaling pathway was discovered in flies and was found to be required for midgut regeneration. Later, this conserved signaling pathway was also found to be essential for regeneration of many mammalian tissues, including heart, liver, skin, and lung, and intestine.Annelids
Many annelids are capable of regeneration. For example, Chaetopterus variopedatus and Branchiomma nigromaculata can regenerate both anterior and posterior body parts after latitudinal bisection. The relationship between somatic and germline stem cell regeneration has been studied at the molecular level in the annelid Capitella teleta. Leeches, however, appear incapable of segmental regeneration. Furthermore, their close relatives, the branchiobdellids, are also incapable of segmental regeneration. However, certain individuals, like the lumbriculids, can regenerate from only a few segments. Segmental regeneration in these animals is epimorphic and occurs through blastema formation. Segmental regeneration has been gained and lost during annelid evolution, as seen in oligochaetes, where head regeneration has been lost three separate times.Along with epimorphosis, some polychaetes like Sabella pavonina experience morphallactic regeneration. Morphallaxis involves the de-differentiation, transformation, and re-differentation of cells to regenerate tissues. How prominent morphallactic regeneration is in oligochaetes is currently not well understood. Although relatively under-reported, it is possible that morphallaxis is a common mode of inter-segment regeneration in annelids. Following regeneration in L. variegatus, past posterior segments sometimes become anterior in the new body orientation, consistent with morphallaxis.
Following amputation, most annelids are capable of sealing their body via rapid muscular contraction. Constriction of body muscle can lead to infection prevention. In certain species, such as Limnodrilus, autolysis can be seen within hours after amputation in the ectoderm and mesoderm. Amputation is also thought to cause a large migration of cells to the injury site, and these form a wound plug.