ISL1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.{{cite journal | vauthors = Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, Donis-Keller H, Permutt MA | display-authors = 6 | 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 = 935–941 | date = July 1994 | pmid = 7912209 | doi = 10.2337/diabetes.43.7.935 | author-link7 = Helen Donis-Keller }}

{{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}}

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 results in failure to undergo neural tube motor neuron differentiation.

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.{{cite journal | vauthors = Gay F, Anglade I, Gong Z, Salbert G | title = The LIM/homeodomain protein islet-1 modulates estrogen receptor functions | journal = Molecular Endocrinology | volume = 14 | issue = 10 | pages = 1627–1648 | date = October 2000 | pmid = 11043578 | doi = 10.1210/mend.14.10.0538 | doi-access = free }}

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. The biological function of ISL1 is demonstrated through ISL1 mutant mice and chick embryos that have altered cell proliferation, survival, and migration of cardiogenic precursors and severe cardiac defects.{{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 = Developmental Cell | volume = 5 | issue = 6 | pages = 877–889 | date = December 2003 | pmid = 14667410 | pmc = 5578462 | doi = 10.1016/s1534-5807(03)00363-0 }} 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.{{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 | display-authors = 6 | title = Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification | journal = Cell | volume = 127 | issue = 6 | pages = 1151–1165 | date = December 2006 | pmid = 17123592 | doi = 10.1016/j.cell.2006.10.029 | s2cid = 31238870 | doi-access = free }}{{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 | display-authors = 6 | title = Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages | journal = Nature | volume = 433 | issue = 7026 | pages = 647–653 | date = February 2005 | pmid = 15703750 | pmc = 5578466 | doi = 10.1038/nature03215 | bibcode = 2005Natur.433..647L }}{{cite journal | vauthors = Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR | display-authors = 6 | title = Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages | journal = Nature | volume = 460 | issue = 7251 | pages = 113–117 | date = July 2009 | pmid = 19571884 | doi = 10.1038/nature08191 | s2cid = 801804 | bibcode = 2009Natur.460..113B }} Research has shown that ISL1 promotes differentiation of cardiac cells and a depletion of ISL1 can respecify the cell fate of nascent cardiomyocytes, such as from ventricular to an atrial identity. {{cite journal | vauthors = Quaranta R, Fell J, Rühle F, Rao J, Piccini I, Araúzo-Bravo MJ, Verkerk AO, Stoll M, Greber B | display-authors = 6 | title = Revised roles of ISL1 in a hES cell-based model of human heart chamber specification | journal = eLife | volume = 7 | date = January 2018 | pmid = 29337667 | doi = 10.7554/eLife.31706 | pmc = 5770158 | doi-access = free }}

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.{{cite journal | vauthors = Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, Schrepfer S, Evans SM, Carrier L, Eschenhagen T | display-authors = 6 | title = Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart | journal = Circulation Research | volume = 110 | issue = 10 | pages = 1303–1310 | date = May 2012 | pmid = 22427341 | pmc = 5559221 | doi = 10.1161/CIRCRESAHA.111.259630 }} Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.{{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 = Circulation Research | volume = 110 | issue = 7 | pages = 922–926 | date = March 2012 | pmid = 22394517 | pmc = 3355870 | doi = 10.1161/CIRCRESAHA.112.266510 }} This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.{{cite journal | vauthors = Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, Schwartz K, Fiszman MY, Vilquin JT | display-authors = 6 | title = Distinction between two populations of islet-1-positive cells in hearts of different murine strains | journal = Stem Cells and Development | volume = 20 | issue = 6 | pages = 1043–1052 | date = June 2011 | pmid = 20942609 | pmc = 5880329 | doi = 10.1089/scd.2010.0374 }} 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 clinical relevance has been seriously questioned.

References

External links

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

Category:Transcription factors