Epimorphosis

Thomas Hunt Morgan, an evolutionary biologist who also worked with embryology, argued that limb and tissue reformation bore many similarities to embryonic development.{{cite journal | vauthors = Sunderland ME | title = Regeneration: Thomas Hunt Morgan's window into development | journal = Journal of the History of Biology | volume = 43 | issue = 2 | pages = 325–61 | date = 2010-05-01 | pmid = 20665231 | doi = 10.1007/s10739-009-9203-2 | s2cid = 24804711 }} Building off of the work of German embryologist Wilhelm Roux, who suggested regeneration was two cooperative but distinct pathways instead of one, Morgan named the two parts of the regenerative process epimorphosis and morphallaxis. Specifically, Morgan wanted epimorphosis to specify the process of entirely new tissues being regrown from an amputation or similar injury, with morphallaxis being coined to describe regeneration that did not use cell proliferation, such as in hydra.{{cite encyclopedia | url = https://embryo.asu.edu/pages/thomas-hunt-morgans-definition-regeneration-morphallaxis-and-epimorphosis | title = Thomas Hunt Morgan's Definition of Regeneration: Morphallaxis and Epimorphosis | encyclopedia = The Embryo Project Encyclopedia | access-date = 2018-02-19 }} The key difference between the two forms of regeneration is that epimorphosis involves cellular proliferation and blastema formation, whereas morphallaxis does not.

File:Limb bud diagram.jpg in embryonic development is very similar to the apical ectodermal cap in limb regeneration. The progress zone can be seen near to the zone of polarizing activity, which instructs cells on how to orient the limb.{{cite journal | vauthors = Summerbell D, Lewis JH, Wolpert L | title = Positional information in chick limb morphogenesis | journal = Nature | volume = 244 | issue = 5417 | pages = 492–6 | date = August 1973 | pmid = 4621272 | doi = 10.1038/244492a0 | bibcode = 1973Natur.244..492S | s2cid = 4166243 }}]]

In vertebrates, epimorphosis relies on blastema formation to proliferate cells into the new tissue. Through studies involving zebrafish fins, the toetips of mice, and limb regeneration in axolotls, researchers at the Polish Academy of Sciences found evidence for epimorphosis occurring in a variety of vertebrates, including instances of mammal epimorphosis.{{Cite book |title=Animal models for the study of human disease | last = Conn | first = P. Michael | name-list-style = vanc | isbn = 978-0-12-809699-4 | edition = Second | location = London, United Kingdom | oclc = 992170104 | date = 2017-06-20 }}

Limb regeneration occurs when a part of an organism is destroyed, and the organism must reform that structure. The general steps for limb regeneration are as follows: epidermis covers the wound which is called the wound healing process,{{cite journal | vauthors = Reddien PW, Sánchez Alvarado A | title = Fundamentals of planarian regeneration | journal = Annual Review of Cell and Developmental Biology | volume = 20 | issue = 1 | pages = 725–57 | date = 2004-10-08 | pmid = 15473858 | doi = 10.1146/annurev.cellbio.20.010403.095114 }} the mesenchyme dedifferentiates into a blastema and a apical ectodermal cap forms, and the limb re-differentiates to form the full limb.{{cite journal | vauthors = Yokoyama H | title = Initiation of limb regeneration: the critical steps for regenerative capacity | journal = Development, Growth & Differentiation | volume = 50 | issue = 1 | pages = 13–22 | date = January 2008 | pmid = 17986260 | doi = 10.1111/j.1440-169X.2007.00973.x | s2cid = 25299267 | doi-access = free }}

Epidermal cells at the wound margins migrate to cover the wound and will become the wound epidermis.{{cite book|title=Developmental Biology|last=Gilbert|first=Scott F.|publisher=Sinauer Associates, Inc.|year=2014|edition=Tenth|location=Sunderland, MA, USA|pages=571–573|name-list-style=vanc}} No scar tissue forms, as it would in mammals. The mesenchymal tissues of the limb stump secrete matrix metalloproteinases (MMPs).{{cite journal | vauthors = Yokoyama H | title = Initiation of limb regeneration: the critical steps for regenerative capacity | journal = Development, Growth & Differentiation | volume = 50 | issue = 1 | pages = 13–22 | date = January 2008 | pmid = 17986260 | doi = 10.1111/j.1440-169X.2007.00973.x | s2cid = 25299267 | doi-access = free }} As the MMPs are secreted, the wound epithelium thickensand eventually becomes an apical ectodermal cap (AEC) that forms on the tip of the stump.{{cite book|title=Issues in Biological, Biochemical, and Evolutionary Sciences Research|publisher=ScholarlyEditions|year=2012|location=Atlanta, GA|pages=464}} This is similar to the embryonic apical ectodermal ridge, which forms during normal limb development. Under the AEC, the nerves near the site of the limb destroyed are degraded.{{Cite journal| vauthors = Chernoff EA, Stocum DL |date= April 1995 |title=Developmental aspects of spinal cord and limb regeneration |journal=Development, Growth and Differentiation|volume=37|issue=2|pages=133–147|doi=10.1046/j.1440-169x.1995.t01-1-00002.x|pmid= 37281907 |s2cid= 83821328 |issn=0012-1592|doi-access=free}} The AEC causes the progress zone to re-establish; this means the cells under the AEC (including bone, cartilage, fibroblast cells, etc) dedifferentiate and become separated mesenchymal cells that form the blastema. Some tissues express specialized genes (like muscle cells) and so if there is damage to these tissues, the genes become downregulated and the proliferation genes are unregulated. The AEC also releases fibroblast growth factors (FGFs) (including FGF-4 and -8) that drive the development of the new limb, essentially resetting the limb back to its embryonic development stage.{{cite journal | vauthors = Nye HL, Cameron JA, Chernoff EA, Stocum DL | title = Regeneration of the urodele limb: a review | journal = Developmental Dynamics | volume = 226 | issue = 2 | pages = 280–94 | date = February 2003 | pmid = 12557206 | doi = 10.1002/dvdy.10236 | s2cid = 28442979 | doi-access = free }} However, even though some of the limb cells are able to dedifferentiate, they are not able to fully dedifferentiate to the level of multipotent progenitor cells. During regeneration, only cartilage cells can form new cartilage tissue, only muscle cells can form new muscle tissue, and so on. The dedifferentiated cells still retain their original specification. To begin the physical formation of a new limb, regeneration occurs in a distal to proximal sequence.{{cite journal | vauthors = Agata K, Saito Y, Nakajima E | title = Unifying principles of regeneration I: Epimorphosis versus morphallaxis | journal = Development, Growth & Differentiation | volume = 49 | issue = 2 | pages = 73–8 | date = February 2007 | pmid = 17335428 | doi = 10.1111/j.1440-169X.2007.00919.x | doi-access = free }} The distal part of the limb is established first, and then the distal part of the limb interacts with the original proximal part of the limb to form the intermediate portion of the limb known as intercalation.

The American cockroach is capable of regenerating limbs that have been damaged or destroyed, such as legs and antennae, as well parts of its compound eye. It does this with lectin—a protein made for binding proteins—named regenectin, which shares a family with other lipopolysaccharide (LPS) binding proteins. Regenectin carries both a regenerative and a system defense function, and it is produced by the cockroach's paracrine system to work with muscle reformation.{{cite journal|vauthors=Kubo T, Arai T|date=September 1996|title=Insect Lectins and Epimorphosis|url=https://www.jstage.jst.go.jp/article/tigg1989/8/43/8_43_357/_pdf/-char/en|journal=Trends in Glycoscience and Glycotechnology|volume=8|issue=43|pages=357–364|doi=10.4052/tigg.8.357|doi-access=free}}

C. teleta is a segmented worm found in North America that is capable of regenerating posterior segments after amputation.{{cite journal | vauthors = Fröbius AC, Matus DQ, Seaver EC | title = Genomic organization and expression demonstrate spatial and temporal Hox gene colinearity in the lophotrochozoan Capitella sp. I | journal = PLOS ONE | volume = 3 | issue = 12 | pages = e4004 | date = 2008-12-23 | pmid = 19104667 | pmc = 2603591 | doi = 10.1371/journal.pone.0004004 | bibcode = 2008PLoSO...3.4004F | doi-access = free }} This regeneration uses the interaction of several sets of Hox genes, as well as blastema formation. All of the Hox genes concerned in epimorphosis are present in the abdominal area of the worm, but not in the anterior portion. However, the genes do not, themselves, direct the anterior-posterior patterning of the worm's thorax.{{cite journal | vauthors = de Jong DM, Seaver EC | title = A Stable Thoracic Hox Code and Epimorphosis Characterize Posterior Regeneration in Capitella teleta | journal = PLOS ONE | volume = 11 | issue = 2 | pages = e0149724 | date = 2016-02-19 | pmid = 26894631 | pmc = 4764619 | doi = 10.1371/journal.pone.0149724 | bibcode = 2016PLoSO..1149724D | doi-access = free }}

P. vitta is a flatworm of genus Planaria that, when needed, can draw upon both morphallaxis and epimorphosis to regrow itself; in P. vitta, epimorphosis precedes morphallaxis and lasts about ten days. Planaria begin epimorphosis by the epidermis contracting immediately after the worm is cut at the head as a predator reactionary mechanism in order to decrease the surface area at the site of the cut.{{cite journal | vauthors = Newmark PA, Sánchez Alvarado A | title = Not your father's planarian: a classic model enters the era of functional genomics | journal = Nature Reviews. Genetics | volume = 3 | issue = 3 | pages = 210–9 | date = March 2002 | pmid = 11972158 | doi = 10.1038/nrg759 | s2cid = 28379017 }}{{Cite journal |last=Chandebois |first= Rosine | name-list-style = vanc |date= August 1980 |title=The Dynamics of Wound Closure and Its Role in the Programming of Planarian Regeneration. II - Distalization |journal=Development, Growth and Differentiation|volume=22|issue=4|pages=693–704|doi=10.1111/j.1440-169x.1980.00693.x|pmid= 37281333 |issn=0012-1592|doi-access=free}} This mechanism activates the neoblasts which are totipotent stems cells{{cite journal | vauthors = Reddien PW, Sánchez Alvarado A | title = Fundamentals of planarian regeneration | journal = Annual Review of Cell and Developmental Biology | volume = 20 | issue = 1 | pages = 725–57 | date = November 2004 | pmid = 15473858 | doi = 10.1146/annurev.cellbio.20.010403.095114 }} which allows rhabdites to secrete materials to make a protective mucosal covering and epithelium to gather at the site through spreading of the cells rather than proliferation that occurs in vertebrates The dorsal and ventral epithelial cells then come to the site and become differentiated to begin regeneration.{{cite journal | vauthors = Sánchez Alvarado A, Newmark PA | title = The use of planarians to dissect the molecular basis of metazoan regeneration | journal = Wound Repair and Regeneration | volume = 6 | issue = 4 | pages = 413–20 | date = July 1998 | pmid = 9824561 | doi = 10.1046/j.1524-475x.1998.60418.x | s2cid = 8085897 }} The polarity of the planaria can be reestablished through an anterior-posterior gradient through Wnt/β-catenin signaling pathway.{{Cite journal|last=Morgan|first=Thomas | name-list-style = vanc |date=1901|title=Regeneration |journal=The American Historical Review |volume=VII |doi=10.1086/ahr/17.4.809 }} Polarity can be described in planarians that the anterior part of the wound site will create a head of a planaria, and the posterior side will create the tail.

{{reflist}}

Category:Developmental biology

Category:Animal anatomy