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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Insulin gene enhancer protein ISL-1''' is a [[protein]] that in humans is encoded by the ''isl1'' [[gene]].<ref name="pmid7912209">{{cite journal | vauthors = Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, Donis-Keller H, Permutt MA | title = Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected] | journal = Diabetes | volume = 43 | issue = 7 | pages = 935–41 | date = July 1994 | pmid = 7912209 | pmc =  | doi = 10.2337/diabetes.43.7.935 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3670| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==  Function ==
{{GNF_Protein_box
| image = PBB_Protein_ISL1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1bw5.
| PDB = {{PDB2|1bw5}}
| Name = ISL1 transcription factor, LIM/homeodomain, (islet-1)
| HGNCid = 6132
| Symbol = ISL1
| AltSymbols =; Isl-1
| OMIM = 600366
| ECnumber = 
| Homologene = 1661
| MGIid = 101791
| GeneAtlas_image1 = PBB_GE_ISL1_206104_at_tn.png
  | Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0003702 |text = RNA polymerase II transcription factor activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006091 |text = generation of precursor metabolites and energy}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0007507 |text = heart development}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3670
    | Hs_Ensembl = ENSG00000016082
    | Hs_RefseqProtein = NP_002193
    | Hs_RefseqmRNA = NM_002202
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 50714715
    | Hs_GenLoc_end = 50726024
    | Hs_Uniprot = P61371
    | Mm_EntrezGene = 16392
    | Mm_Ensembl = ENSMUSG00000042258
    | Mm_RefseqmRNA = NM_021459
    | Mm_RefseqProtein = NP_067434
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 117418963
    | Mm_GenLoc_end = 117430370
    | Mm_Uniprot = Q8BTH7
  }}
}}
'''ISL1 transcription factor, LIM/homeodomain, (islet-1)''', also known as '''ISL1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3670| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a [[transcription factor]] containing two [[N-terminal]] [[LIM domain]]s and one [[C-terminal]] [[homeodomain]]. The encoded protein plays an important role in the [[embryogenesis]] of pancreatic [[islets of Langerhans]]. In mouse embryos, a deficiency of this gene fail to undergo neural tube motor neuron differentiation.<ref name="entrez" />
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a transcription factor containing two N-terminal LIM domains and one C-terminal homeodomain. The encoded protein plays an important role in the embryogenesis of pancreatic islets of Langerhans. In mouse embryos, a deficiency of this gene fail to undergo neural tube motor neuron differentiation.<ref name="entrez">{{cite web | title = Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3670| accessdate = }}</ref>
}}


==References==
== Interactions ==
{{reflist|2}}
 
==Further reading==
ISL1 has been shown to [[Protein-protein interaction|interact]] with [[Estrogen receptor alpha]].<ref name="pmid11043578">{{cite journal | vauthors = Gay F, Anglade I, Gong Z, Salbert G | title = The LIM/homeodomain protein islet-1 modulates estrogen receptor functions | journal = Mol. Endocrinol. | volume = 14 | issue = 10 | pages = 1627–48 | date = October 2000 | pmid = 11043578 | doi = 10.1210/me.14.10.1627 }}</ref>
 
== Role in cardiac development ==
 
ISL1 is a marker for cardiac progenitors of the [[secondary heart field]] (SHF) which includes the right ventricle and the outflow tract. It also has a biological function as shown in Isl1 knockout mice which have a severely deformed heart.<ref name="pmid14667410">{{cite journal | vauthors = Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S | title = Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart | journal = Dev. Cell | volume = 5 | issue = 6 | pages = 877–89 | date = December 2003 | pmid = 14667410 | doi = 10.1016/S1534-5807(03)00363-0 }}</ref> More recently it has been defined as a marker for a cardiac progenitor cell lineage that is capable of differentiating into all 3 major cell types of the heart: [[cardiomyocytes]], [[smooth muscle]] and [[endothelial]] cell lineages.<ref name="pmid17123592">{{cite journal | vauthors = Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR | title = Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification | journal = Cell | volume = 127 | issue = 6 | pages = 1151–65 | date = December 2006 | pmid = 17123592 | doi = 10.1016/j.cell.2006.10.029 }}</ref><ref name="pmid15703750">{{cite journal | vauthors = Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR | title = Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages | journal = Nature | volume = 433 | issue = 7026 | pages = 647–53 | date = February 2005 | pmid = 15703750 | doi = 10.1038/nature03215 }}</ref><ref name="pmid19571884">{{cite journal | vauthors = Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR | title = Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages | journal = Nature | volume = 460 | issue = 7251 | pages = 113–7 | date = July 2009 | pmid = 19571884 | doi = 10.1038/nature08191 }}</ref>
 
The validity of ISL1 as a marker for cardiac progenitor cells has been questioned since some groups have found no evidence that ISL1 cells serve as cardiac progenitors.<ref name="pmid22427341">{{cite journal | vauthors = Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, Schrepfer S, Evans SM, Carrier L, Eschenhagen T | title = Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart | journal = Circ. Res. | volume = 110 | issue = 10 | pages = 1303–10 | date = May 2012 | pmid = 22427341 | doi = 10.1161/CIRCRESAHA.111.259630 }}</ref> Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac [[neural crest]].<ref name="pmid22394517">{{cite journal | vauthors = Engleka KA, Manderfield LJ, Brust RD, Li L, Cohen A, Dymecki SM, Epstein JA | title = Islet1 derivatives in the heart are of both neural crest and second heart field origin | journal = Circ. Res. | volume = 110 | issue = 7 | pages = 922–6 | date = March 2012 | pmid = 22394517 | doi = 10.1161/CIRCRESAHA.112.266510 | pmc = 3355870 }}</ref> This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.<ref name="pmid20942609">{{cite journal | vauthors = Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, Schwartz K, Fiszman MY, Vilquin JT | title = Distinction between two populations of islet-1-positive cells in hearts of different murine strains | journal = Stem Cells Dev. | volume = 20 | issue = 6 | pages = 1043–52 | date = June 2011 | pmid = 20942609 | doi = 10.1089/scd.2010.0374 }}</ref> While it has been demonstrated by multiple groups that ISL1-positive cells can indeed differentiate into all 3 major cell types of the heart, their significance in cardiovascular development is still unclear and their clinical relevance has been seriously questioned.
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Larsson LI | title = On the development of the islets of Langerhans | journal = Microsc. Res. Tech. | volume = 43 | issue = 4 | pages = 284–91 | year = 1999 | pmid = 9849969 | doi = 10.1002/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0 }}
| citations =
* {{cite journal | vauthors = Dong J, Asa SL, Drucker DJ | title = Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1 | journal = Mol. Endocrinol. | volume = 5 | issue = 11 | pages = 1633–41 | year = 1992 | pmid = 1685766 | doi = 10.1210/mend-5-11-1633 }}
*{{cite journal | author=Larsson LI |title=On the development of the islets of Langerhans. |journal=Microsc. Res. Tech. |volume=43 |issue= 4 |pages= 284-91 |year= 1999 |pmid= 9849969 |doi= 10.1002/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0 }}
* {{cite journal | vauthors = Riggs AC, Tanizawa Y, Aoki M, Wasson J, Ferrer J, Rabin DU, Vaxillaire M, Froguel P, Permutt MA | title = Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM | journal = Diabetes | volume = 44 | issue = 6 | pages = 689–94 | year = 1995 | pmid = 7789634 | doi = 10.2337/diabetes.44.6.689 }}
*{{cite journal | author=Dong J, Asa SL, Drucker DJ |title=Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1. |journal=Mol. Endocrinol. |volume=5 |issue= 11 |pages= 1633-41 |year= 1992 |pmid= 1685766 |doi= }}
* {{cite journal | vauthors = Wang M, Drucker DJ | title = The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage | journal = Endocrinology | volume = 134 | issue = 3 | pages = 1416–22 | year = 1994 | pmid = 7907017 | doi = 10.1210/en.134.3.1416 }}
*{{cite journal | author=Riggs AC, Tanizawa Y, Aoki M, ''et al.'' |title=Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM. |journal=Diabetes |volume=44 |issue= 6 |pages= 689-94 |year= 1995 |pmid= 7789634 |doi= }}
* {{cite journal | vauthors = Pfaff SL, Mendelsohn M, Stewart CL, Edlund T, Jessell TM | title = Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation | journal = Cell | volume = 84 | issue = 2 | pages = 309–20 | year = 1996 | pmid = 8565076 | doi = 10.1016/S0092-8674(00)80985-X }}
*{{cite journal | author=Wang M, Drucker DJ |title=The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage. |journal=Endocrinology |volume=134 |issue= 3 |pages= 1416-22 |year= 1994 |pmid= 7907017 |doi= }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Res. | volume = 6 | issue = 9 | pages = 791–806 | year = 1997 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
*{{cite journal  | author=Tanizawa Y, Riggs AC, Dagogo-Jack S, ''et al.'' |title=Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected] |journal=Diabetes |volume=43 |issue= 7 |pages= 935-41 |year= 1994 |pmid= 7912209 |doi=  }}
* {{cite journal | vauthors = Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H | title = Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells | journal = Nature | volume = 385 | issue = 6613 | pages = 257–60 | year = 1997 | pmid = 9000074 | doi = 10.1038/385257a0 }}
*{{cite journal | author=Pfaff SL, Mendelsohn M, Stewart CL, ''et al.'' |title=Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. |journal=Cell |volume=84 |issue= 2 |pages= 309-20 |year= 1996 |pmid= 8565076 |doi= }}
* {{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 = J. Biol. Chem. | volume = 273 | issue = 6 | pages = 3152–7 | year = 1998 | pmid = 9452425 | doi = 10.1074/jbc.273.6.3152 }}
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
* {{cite journal | vauthors = Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG | title = RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex | journal = Nat. Genet. | volume = 22 | issue = 4 | pages = 394–9 | year = 1999 | pmid = 10431247 | doi = 10.1038/11970 }}
*{{cite journal | author=Ahlgren U, Pfaff SL, Jessell TM, ''et al.'' |title=Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. |journal=Nature |volume=385 |issue= 6613 |pages= 257-60 |year= 1997 |pmid= 9000074 |doi= 10.1038/385257a0 }}
* {{cite journal | vauthors = Gay F, Anglade I, Gong Z, Salbert G | title = The LIM/homeodomain protein islet-1 modulates estrogen receptor functions | journal = Mol. Endocrinol. | volume = 14 | issue = 10 | pages = 1627–48 | year = 2001 | pmid = 11043578 | doi = 10.1210/me.14.10.1627 }}
*{{cite journal | author=Jurata LW, Pfaff SL, Gill GN |title=The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors. |journal=J. Biol. Chem. |volume=273 |issue= 6 |pages= 3152-7 |year= 1998 |pmid= 9452425 |doi= }}
* {{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 | year = 2002 | pmid = 11882901 | doi = 10.1038/416099a }}
*{{cite journal | author=Bach I, Rodriguez-Esteban C, Carrière C, ''et al.'' |title=RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. |journal=Nat. Genet. |volume=22 |issue= 4 |pages= 394-9 |year= 1999 |pmid= 10431247 |doi= 10.1038/11970 }}
* {{cite journal | vauthors = Holm P, Rydlander B, Luthman H, Kockum I, ((European Consortium for IDDM Genome Studies)) | title = Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families | journal = Diabetes | volume = 53 | issue = 6 | pages = 1584–91 | year = 2004 | pmid = 15161765 | doi = 10.2337/diabetes.53.6.1584}}
*{{cite journal | author=Gay F, Anglade I, Gong Z, Salbert G |title=The LIM/homeodomain protein islet-1 modulates estrogen receptor functions. |journal=Mol. Endocrinol. |volume=14 |issue= 10 |pages= 1627-48 |year= 2001 |pmid= 11043578 |doi= }}
* {{cite journal | vauthors = Hori Y, Gu X, Xie X, Kim SK | title = Differentiation of insulin-producing cells from human neural progenitor cells | journal = PLoS Med. | volume = 2 | issue = 4 | pages = e103 | year = 2006 | pmid = 15839736 | pmc = 1087208 | doi = 10.1371/journal.pmed.0020103 }}
*{{cite journal | author=Ostendorff HP, Peirano RI, Peters MA, ''et al.'' |title=Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors. |journal=Nature |volume=416 |issue= 6876 |pages= 99-103 |year= 2002 |pmid= 11882901 |doi= 10.1038/416099a }}
* {{cite journal | vauthors = Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, Heidt AB, Mori AD, Arruda EP, Gertsenstein M, Georges R, Davidson L, Mo R, Hui CC, Henkelman RM, Nemer M, Black BL, Nagy A, Bruneau BG | title = Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development | journal = Development | volume = 132 | issue = 10 | pages = 2463–74 | year = 2005 | pmid = 15843409 | doi = 10.1242/dev.01827 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Peng SY, Wang WP, Meng J, Li T, Zhang H, Li YM, Chen P, Ma KT, Zhou CY | title = ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells | journal = Biochim. Biophys. Acta | volume = 1731 | issue = 3 | pages = 154–9 | year = 2006 | pmid = 16321656 | doi = 10.1016/j.bbaexp.2005.08.013 }}
*{{cite journal  | author=Holm P, Rydlander B, Luthman H, ''et al.'' |title=Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families. |journal=Diabetes |volume=53 |issue= 6 |pages= 1584-91 |year= 2004 |pmid= 15161765 |doi= }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal | author=Hori Y, Gu X, Xie X, Kim SK |title=Differentiation of insulin-producing cells from human neural progenitor cells. |journal=PLoS Med. |volume=2 |issue= 4 |pages= e103 |year= 2006 |pmid= 15839736 |doi= 10.1371/journal.pmed.0020103 }}
*{{cite journal | author=Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, ''et al.'' |title=Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. |journal=Development |volume=132 |issue= 10 |pages= 2463-74 |year= 2005 |pmid= 15843409 |doi= 10.1242/dev.01827 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal  | author=Peng SY, Wang WP, Meng J, ''et al.'' |title=ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells. |journal=Biochim. Biophys. Acta |volume=1731 |issue= 3 |pages= 154-9 |year= 2006 |pmid= 16321656 |doi= 10.1016/j.bbaexp.2005.08.013 }}
}}
{{refend}}
{{refend}}


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* {{MeshName|ISL1+protein,+human}}
* {{MeshName|ISL1+protein,+human}}


{{PDB Gallery|geneid=3670}}
{{Transcription factors}}
{{NLM content}}


{{protein-stub}}
{{NLM content}}
{{Transcription factors}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Latest revision as of 21:18, 15 May 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the isl1 gene.[1][2]

Function

This gene encodes a transcription factor containing two N-terminal LIM domains and one C-terminal homeodomain. The encoded protein plays an important role in the embryogenesis of pancreatic islets of Langerhans. In mouse embryos, a deficiency of this gene fail to undergo neural tube motor neuron differentiation.[2]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.[3]

Role in cardiac development

ISL1 is a marker for cardiac progenitors of the secondary heart field (SHF) which includes the right ventricle and the outflow tract. It also has a biological function as shown in Isl1 knockout mice which have a severely deformed heart.[4] More recently it has been defined as a marker for a cardiac progenitor cell lineage that is capable of differentiating into all 3 major cell types of the heart: cardiomyocytes, smooth muscle and endothelial cell lineages.[5][6][7]

The validity of ISL1 as a marker for cardiac progenitor cells has been questioned since some groups have found no evidence that ISL1 cells serve as cardiac progenitors.[8] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.[9] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.[10] While it has been demonstrated by multiple groups that ISL1-positive cells can indeed differentiate into all 3 major cell types of the heart, their significance in cardiovascular development is still unclear and their clinical relevance has been seriously questioned.

References

  1. Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, Donis-Keller H, Permutt MA (July 1994). "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]". Diabetes. 43 (7): 935–41. doi:10.2337/diabetes.43.7.935. PMID 7912209.
  2. 2.0 2.1 "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
  3. Gay F, Anglade I, Gong Z, Salbert G (October 2000). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Mol. Endocrinol. 14 (10): 1627–48. doi:10.1210/me.14.10.1627. PMID 11043578.
  4. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S (December 2003). "Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart". Dev. Cell. 5 (6): 877–89. doi:10.1016/S1534-5807(03)00363-0. PMID 14667410.
  5. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR (December 2006). "Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification". Cell. 127 (6): 1151–65. doi:10.1016/j.cell.2006.10.029. PMID 17123592.
  6. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (February 2005). "Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages". Nature. 433 (7026): 647–53. doi:10.1038/nature03215. PMID 15703750.
  7. Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR (July 2009). "Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages". Nature. 460 (7251): 113–7. doi:10.1038/nature08191. PMID 19571884.
  8. Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, Schrepfer S, Evans SM, Carrier L, Eschenhagen T (May 2012). "Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart". Circ. Res. 110 (10): 1303–10. doi:10.1161/CIRCRESAHA.111.259630. PMID 22427341.
  9. Engleka KA, Manderfield LJ, Brust RD, Li L, Cohen A, Dymecki SM, Epstein JA (March 2012). "Islet1 derivatives in the heart are of both neural crest and second heart field origin". Circ. Res. 110 (7): 922–6. doi:10.1161/CIRCRESAHA.112.266510. PMC 3355870. PMID 22394517.
  10. Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, Schwartz K, Fiszman MY, Vilquin JT (June 2011). "Distinction between two populations of islet-1-positive cells in hearts of different murine strains". Stem Cells Dev. 20 (6): 1043–52. doi:10.1089/scd.2010.0374. PMID 20942609.

Further reading

  • Larsson LI (1999). "On the development of the islets of Langerhans". Microsc. Res. Tech. 43 (4): 284–91. doi:10.1002/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0. PMID 9849969.
  • Dong J, Asa SL, Drucker DJ (1992). "Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1". Mol. Endocrinol. 5 (11): 1633–41. doi:10.1210/mend-5-11-1633. PMID 1685766.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.