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===Regeneration=== Zebrafish have the ability to [[Regeneration (biology)|regenerate]] their heart and [[lateral line]] [[hair cell]]s during their larval stages.<ref name=Wade>{{cite news |title=Research Offers Clue Into How Hearts Can Regenerate in Some Species |last=Wade |first=Nicholas |work=The New York Times |date=March 24, 2010 |url=https://www.nytimes.com/2010/03/25/science/25heart.html |archive-url=https://ghostarchive.org/archive/20220101/https://www.nytimes.com/2010/03/25/science/25heart.html |archive-date=2022-01-01 |url-access=limited}}{{cbignore}}</ref><ref name="autogenerated1187">{{cite journal |vauthors=Lush ME, Piotrowski T |title=Sensory hair cell regeneration in the zebrafish lateral line |journal=Developmental Dynamics |volume=243 |issue=10 |pages=1187–1202 |date=October 2014 |pmid=25045019 |pmc=4177345 |doi=10.1002/dvdy.24167}}</ref> The cardiac regenerative process likely involves signaling pathways such as [[Notch signaling pathway|Notch]] and [[Wnt signaling pathway|Wnt]]; hemodynamic changes in the damaged heart are sensed by ventricular [[Endothelium|endothelial cells]] and their associated cardiac cilia by way of the mechanosensitive ion channel [[TRPV4]], subsequently facilitating the [[Notch signaling pathway]] via [[KLF2]] and activating various downstream effectors such as [[Bone morphogenetic protein 2|BMP-2]] and [[HER2/neu]].<ref>{{cite web |last1=Teske |first1=Christopher |title=An Evolving Role for Notch Signaling in Heart Regeneration of the Zebrafish Danio rerio |url=https://www.researchgate.net/publication/362704455 |website=Researchgate.com |access-date=4 October 2022 |archive-date=19 May 2024 |archive-url=https://web.archive.org/web/20240519141133/https://www.researchgate.net/publication/362704455_An_Evolving_Role_for_Notch_Signaling_in_Heart_Regeneration_of_the_Zebrafish_Danio_rerio |url-status=live}}</ref> In 2011, the [[British Heart Foundation]] ran an advertising campaign publicising its intention to study the applicability of this ability to humans, stating that it aimed to raise £50 million in research funding.<ref>{{cite web |url=https://www.youtube.com/watch?v=djFb8PGS34g |archive-url=https://ghostarchive.org/varchive/youtube/20211117/djFb8PGS34g |archive-date=2021-11-17 |url-status=live |title=Mending Broken Hearts (2011) British Heart Foundation TV ad |publisher=[[British Heart Foundation]] via YouTube |date=January 31, 2011 |access-date=November 15, 2012}}{{cbignore}}</ref><ref>{{cite web |url=http://www.bhf.org.uk/research/mending-broken-hearts-appeal/the-science.aspx?pid=p&sc_cid=MBH-EX-24&gclid=CL2w_L2hhqcCFcgf4QodBA25eA |title=British Heart Foundation – The science behind the appeal |publisher=Bhf.org.uk |date=February 16, 2007 |access-date=November 15, 2012 |archive-url=https://web.archive.org/web/20120310000952/http://www.bhf.org.uk/research/mending-broken-hearts-appeal/the-science.aspx?pid=p&sc_cid=MBH-EX-24&gclid=CL2w_L2hhqcCFcgf4QodBA25eA |archive-date=10 March 2012}}</ref> Zebrafish have also been found to regenerate [[photoreceptor cells]] and [[retina]]l neurons following injury, which has been shown to be mediated by the dedifferentiation and proliferation of [[Muller glia|Müller glia]].<ref>{{cite journal |vauthors=Bernardos RL, Barthel LK, Meyers JR, Raymond PA |title=Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells |journal=The Journal of Neuroscience |volume=27 |issue=26 |pages=7028–7040 |date=June 2007 |pmid=17596452 |pmc=6672216 |doi=10.1523/JNEUROSCI.1624-07.2007}}</ref> Researchers frequently [[amputate]] the dorsal and ventral tail fins and analyze their regrowth to test for mutations. It has been found that [[Histone methylation|histone demethylation]] occurs at the site of the amputation, switching the zebrafish's cells to an "active", regenerative, stem cell-like state.<ref>{{cite journal |vauthors=Stewart S, Tsun ZY, Izpisua Belmonte JC |title=A histone demethylase is necessary for regeneration in zebrafish |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 |issue=47 |pages=19889–19894 |date=November 2009 |pmid=19897725 |pmc=2785262 |doi=10.1073/pnas.0904132106 |doi-access=free |bibcode=2009PNAS..10619889S |jstor=25593294}}</ref><ref>{{Cite web |url=https://www.sciencedaily.com/releases/2009/11/091102171419.htm |title=Organ Regeneration In Zebrafish: Unraveling The Mechanisms |website=ScienceDaily |access-date=2018-03-09 |archive-date=2018-02-05 |archive-url=https://web.archive.org/web/20180205130047/https://www.sciencedaily.com/releases/2009/11/091102171419.htm |url-status=live}}</ref> In 2012, Australian scientists published a study revealing that zebrafish use a specialised [[protein]], known as [[fibroblast growth factor]], to ensure their [[spinal cord]]s heal without [[glial scar]]ring after injury.<ref name=Regen2012>{{cite journal |vauthors=Goldshmit Y, Sztal TE, Jusuf PR, Hall TE, Nguyen-Chi M, Currie PD |title=Fgf-dependent glial cell bridges facilitate spinal cord regeneration in zebrafish |journal=The Journal of Neuroscience |volume=32 |issue=22 |pages=7477–7492 |date=May 2012 |pmid=22649227 |pmc=6703582 |doi=10.1523/JNEUROSCI.0758-12.2012}}</ref><ref>{{Cite web |url=http://www.sci-news.com/othersciences/biochemistry/article00366.html |title=Study Reveals Secret of Zebrafish | Biochemistry | Sci-News.com |website=Breaking Science News | Sci-News.com |access-date=2012-06-02 |archive-date=2020-11-11 |archive-url=https://web.archive.org/web/20201111224203/http://www.sci-news.com/othersciences/biochemistry/article00366.html |url-status=live}}</ref> In addition, [[hair cell]]s of the posterior [[lateral line]] have also been found to regenerate following damage or developmental disruption.<ref name="autogenerated1187"/><ref name="autogenerated832">{{cite journal |vauthors=Head JR, Gacioch L, Pennisi M, Meyers JR |title=Activation of canonical Wnt/β-catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line |journal=Developmental Dynamics |volume=242 |issue=7 |pages=832–846 |date=July 2013 |pmid=23606225 |doi=10.1002/dvdy.23973 |doi-access=free}}</ref> Study of gene expression during regeneration has allowed for the identification of several important signaling pathways involved in the process, such as [[Wnt signaling]] and [[Fibroblast growth factor]].<ref name="autogenerated832"/><ref>{{cite journal |vauthors=Steiner AB, Kim T, Cabot V, Hudspeth AJ |title=Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=111 |issue=14 |pages=E1393–E1401 |date=April 2014 |pmid=24706895 |pmc=3986164 |doi=10.1073/pnas.1318692111 |doi-access=free |bibcode=2014PNAS..111E1393S}}</ref> In probing disorders of the nervous system, including neurodegenerative diseases, movement disorders, psychiatric disorders and deafness, researchers are using the zebrafish to understand how the genetic defects underlying these conditions cause functional abnormalities in the human brain, spinal cord and sensory organs.<ref name="Kizil">{{cite journal |vauthors=Kizil C |title=Mechanisms of Pathology-Induced Neural Stem Cell Plasticity and Neural Regeneration in Adult Zebrafish Brain |journal=Current Pathobiology Reports |volume=6 |issue=1 |pages=71–77 |date=January 2018 |pmid=29938129 |pmc=5978899 |doi=10.1007/s40139-018-0158-x}}</ref><ref name="Cosacak">{{cite journal |vauthors=Cosacak MI, Bhattarai P, Reinhardt S, Petzold A, Dahl A, Zhang Y, Kizil C |title=Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity |journal=Cell Reports |volume=27 |issue=4 |pages=1307–1318.e3 |date=April 2019 |pmid=31018142 |doi=10.1016/j.celrep.2019.03.090 |doi-access=free}}</ref><ref name="Bhattarai">{{cite journal |vauthors=Bhattarai P, Cosacak MI, Mashkaryan V, Demir S, Popova SD, Govindarajan N, Brandt K, Zhang Y, Chang W, Ampatzis K, Kizil C |display-authors=6 |title=Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain |journal=PLOS Biology |volume=18 |issue=1 |pages=e3000585 |date=January 2020 |pmid=31905199 |pmc=6964913 |doi=10.1371/journal.pbio.3000585 |doi-access=free}}</ref><ref name="Xi">{{cite journal |vauthors=Xi Y, Noble S, Ekker M |title=Modeling neurodegeneration in zebrafish |journal=Current Neurology and Neuroscience Reports |volume=11 |issue=3 |pages=274–282 |date=June 2011 |pmid=21271309 |pmc=3075402 |doi=10.1007/s11910-011-0182-2}}</ref> Researchers have also studied the zebrafish to gain new insights into the complexities of human musculoskeletal diseases, such as [[muscular dystrophy]].<ref>{{cite journal |vauthors=Bassett DI, Currie PD |title=The zebrafish as a model for muscular dystrophy and congenital myopathy |journal=Human Molecular Genetics |volume=12 |issue=Spec No 2 |pages=R265–R270 |date=October 2003 |pmid=14504264 |doi=10.1093/hmg/ddg279 |doi-access=free}}</ref> Another focus of zebrafish research is to understand how a gene called [[Hedgehog signaling pathway|Hedgehog]], a biological signal that underlies a number of human cancers, controls cell growth.
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