View source for LHX1

{{Infobox_gene}}
'''LIM homeobox 1''' is a [[protein]] that in humans is encoded by the LHX1 [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: LHX1 LIM homeobox 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3975| accessdate = }}</ref>

This [[gene]] encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells. It is also key in development of renal and urogenital systems and is required for normal organogenesis.<ref name=Dormoy>{{cite journal|last1=Dormoy|first1=V.|title=LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma.|journal=Oncogene|date=2011|volume=30|issue=15|pages=1753–1763|display-authors=etal|doi=10.1038/onc.2010.557|pmid=21132009}}</ref> A similar protein in mice is an essential regulator of the vertebrate head organizer.<ref name="entrez"/>

== Function ==

The Lim gene family is a subfamily of homeobox genes.<ref name="Hobert">{{cite journal|last=Hobert|first=Oliver|author2=Heiner Westphal |title=Functions of LIM-homeobox genes|journal=Trends in Genetics|date=February 2000|volume=16|issue=2|pages=75–83|doi=10.1016/S0168-9525(99)01883-1|url=http://www.sciencedirect.com/science/article/pii/S0168952599018831|accessdate=2012-03-29}}</ref>  The homeobox genes are essential in organizing the body plan of an organism and all contain the same conserved homeodomain of amino acids.<ref>{{cite book | last = Carlson | first = Bruce M | title = Human Embryology and Developmental Biology | year = 2009 | publisher = Mosby Elsevier | location = Philadelphia, PA | isbn = 978-0-323-05385-3 | pages = 67–70 | name-list-format = vanc }}</ref>  Evidence that Lim-1 is essential to a developing organism is its conservation throughout evolution and presence in a variety of organisms.<ref name="Hobert" />  The Lim-1 gene encodes a transcription factor which binds to the DNA of specific genes and functions to produce the needed gene product for development of the organism.<ref name=Kobayashi>{{cite journal | vauthors = Kobayashi A, Shawlot W, Kania A, Behringer RR | title = Requirement of Lim1 for female reproductive tract development | journal = Development | volume = 131 | issue = 3 | pages = 539–49 | date = Feb 2004 | pmid = 14695376 | doi = 10.1242/dev.00951 }}</ref> Lim-1 is important during early molecular development and is required in both primitive streak-derived tissue and visceral endoderm of the early embryo for development of a head.<ref name=Shawlot>{{cite journal | vauthors = Shawlot W, Wakamiya M, Kwan KM, Kania A, Jessell TM, Behringer RR | title = Lim1 is required in both primitive streak-derived tissues and visceral endoderm for head formation in the mouse | journal = Development | volume = 126 | issue = 22 | pages = 4925–32 | date = Nov 1999 | pmid = 10529411 | url = http://dev.biologists.org/content/126/22/4925.full.pdf+html }}</ref>  Studies done using mutant organisms without the Lim gene results in organisms that develop no head structure at all support the essential role of the Lim-1 gene in formation of the head.<ref>{{cite journal | vauthors = Bally-Cuif L, Boncinelli E | title = Transcription factors and head formation in vertebrates | journal = BioEssays | volume = 19 | issue = 2 | pages = 127–35 | date = Feb 1997 | pmid = 9046242 | doi = 10.1002/bies.950190207 }}</ref>  This gene has also been shown to play a crucial role in the formation of the female reproductive tract.<ref name="Kobayashi" />  The gene is expressed in the developing Müllerian duct of females, and when the gene is knocked out no reproductive tract forms.<ref name="Kobayashi" /> Recent studies have shown that Lim-1 mutations may be one cause of the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.<ref name=Ledig>{{cite journal | vauthors = Ledig S, Brucker S, Barresi G, Schomburg J, Rall K, Wieacker P | title = Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome | journal = Human Reproduction | volume = 27 | issue = 9 | pages = 2872–5 | date = Sep 2012 | pmid = 22740494 | doi = 10.1093/humrep/des206 }}</ref> MRKH is characterized by defective development, or absence, of the uterus and upper part of the vagina in women with normal ovaries and karyotype.<ref name=Ledig />

Lim-1’s expression is controlled in part by the sonic hedgehog-Gli signaling pathway.<ref name=Dormoy /> Recent studies in mice have shown that Lim-1 silencing halts tumor growth and impairs tumor cell movement via inhibition of protein expression involved in metastatic spread.<ref name=Dormoy /> Therefore, in tumor cells Lim-1 acts as an oncogene.<ref name=Dormoy /> Thus, targeting Lim-1 can be a potential cancer therapy. In addition, Lim-1 is important in rodent renal development.<ref name=Guertl>{{cite journal | vauthors = Guertl B, Senanayake U, Nusshold E, Leuschner I, Mannweiler S, Ebner B, Hoefler G | title = Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas | journal = Pathobiology | volume = 78 | issue = 4 | pages = 210–9 | date = 2011 | pmid = 21778788 | doi = 10.1159/000326769 }}</ref> Lim-1 deficiency results in development of multicystic kidney, whereas, its expression can contribute to pathogenesis of nephroblastomas.<ref name=Guertl /> Also, Lim-1 plays a role in embryonic retinal development.<ref name=Liu>{{cite journal | vauthors = Liu W, Wang JH, Xiang M | title = Specific expression of the LIM/homeodomain protein Lim-1 in horizontal cells during retinogenesis | journal = Developmental Dynamics | volume = 217 | issue = 3 | pages = 320–5 | date = Mar 2000 | pmid = 10741426 | doi = 10.1002/(SICI)1097-0177(200003)217:3<320::AID-DVDY10>3.0.CO;2-F }}</ref> Lim-1 expression affects differentiation and maintenance of horizontal cells located in the retinal, thus, it could serve as a marker in studies of horizontal cell specification.<ref name=Liu />
{{Clear}}

Lim-1 (Lhx1) functions as a transcription factor necessary for regulating the production of coupling factors required for proper communication between the neurons located in the part of the brain responsible for regulation of circadian rhythms called the suprachiasmatic nucleus (SCN).<ref name=Hatori>{{cite journal | vauthors = Hatori M, Gill S, Mure LS, Goulding M, O'Leary DD, Panda S | title = Lhx1 maintains synchrony among circadian oscillator neurons of the SCN | journal = eLife | date = Jul 2014 | doi = 10.7554/eLife.03357 }}</ref> In mouse studies where Lim-1 transcription was restricted at some point during development in utero, the individual units within the subject’s molecular clock functioned properly but were unable to work together.<ref name=Hatori /> Communication of these units is required to match their release of clock proteins which begin a transcription cascade of many other proteins that produce functional responses in tissues.<ref name=Hatori /> The cyclic pattern of these responses is due to the feedback of the clock proteins and consequent changes to this transcription cascade.<ref name=Hatori /> Reduced Lim-1 expression leads to inadequate levels of proteins such as Vasoactive Intestinal Polypeptide (VIP) that work to produce the neuron coordination required for a regulated circadian rhythm.<ref name=Hatori /> The lack of such coupling factors causes the circadian clock to not function properly because the units within the SCN cannot match their release of clock proteins, and therefore their transcriptional cascades of proteins that cause changes in arousal do not align.<ref name=Hatori />

== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Shawlot W, Behringer RR | title = Requirement for Lim1 in head-organizer function | journal = Nature | volume = 374 | issue = 6521 | pages = 425–30 | date = Mar 1995 | pmid = 7700351 | doi = 10.1038/374425a0 }}
* {{cite journal | vauthors = Bozzi F, Bertuzzi S, Strina D, Giannetto C, Vezzoni P, Villa A | title = The exon-intron structure of human LHX1 gene | journal = Biochemical and Biophysical Research Communications | volume = 229 | issue = 2 | pages = 494–7 | date = Dec 1996 | pmid = 8954926 | doi = 10.1006/bbrc.1996.1832 }}
* {{cite journal | vauthors = Dong WF, Heng HH, Lowsky R, Xu Y, DeCoteau JF, Shi XM, Tsui LC, Minden MD | title = Cloning, expression, and chromosomal localization to 11p12-13 of a human LIM/HOMEOBOX gene, hLim-1 | journal = DNA and Cell Biology | volume = 16 | issue = 6 | pages = 671–8 | date = Jun 1997 | pmid = 9212161 | doi = 10.1089/dna.1997.16.671 }}
* {{cite journal | vauthors = Jurata LW, Pfaff SL, Gill GN | title = The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3152–7 | date = Feb 1998 | pmid = 9452425 | doi = 10.1074/jbc.273.6.3152 }}
* {{cite journal | vauthors = Ostendorff HP, Peirano RI, Peters MA, Schlüter A, Bossenz M, Scheffner M, Bach I | title = Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors | journal = Nature | volume = 416 | issue = 6876 | pages = 99–103 | date = Mar 2002 | pmid = 11882901 | doi = 10.1038/416099a }}
* {{cite journal | vauthors = Phillips JC | title = Assignment of LHX1 to human chromosome bands 17q11.2-->q12 by use of radiation hybrid mapping and somatic cell hybridization | journal = Cytogenetic and Genome Research | volume = 97 | issue = 1-2 | pages = 140D | year = 2003 | pmid = 12438757 | doi = 10.1159/000064048 }}
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