ISL1

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.[5] [6]

ISL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesISL1, ISLET1, Isl-1, ISL LIM homeobox 1
External IDsOMIM: 600366 MGI: 101791 HomoloGene: 1661 GeneCards: ISL1
Orthologs
SpeciesHumanMouse
Entrez

3670

16392

Ensembl

ENSG00000016082

ENSMUSG00000042258

UniProt

P61371

P61372

RefSeq (mRNA)

NM_002202

NM_021459

RefSeq (protein)

NP_002193

NP_067434

Location (UCSC)Chr 5: 51.38 – 51.39 MbChr 13: 116.43 – 116.45 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[6]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.[7]

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.[8] 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.[9][10][11] 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. [12]

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.[13] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.[14] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.[15] 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. GRCh38: Ensembl release 89: ENSG00000016082 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000042258 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, et al. (July 1994). "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]". Diabetes. 43 (7): 935–941. doi:10.2337/diabetes.43.7.935. PMID 7912209.
  6. "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
  7. Gay F, Anglade I, Gong Z, Salbert G (October 2000). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Molecular Endocrinology. 14 (10): 1627–1648. doi:10.1210/mend.14.10.0538. PMID 11043578.
  8. 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". Developmental Cell. 5 (6): 877–889. doi:10.1016/s1534-5807(03)00363-0. PMC 5578462. PMID 14667410.
  9. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, et al. (December 2006). "Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification". Cell. 127 (6): 1151–1165. doi:10.1016/j.cell.2006.10.029. PMID 17123592. S2CID 31238870.
  10. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, et al. (February 2005). "Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages". Nature. 433 (7026): 647–653. Bibcode:2005Natur.433..647L. doi:10.1038/nature03215. PMC 5578466. PMID 15703750.
  11. Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, et al. (July 2009). "Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages". Nature. 460 (7251): 113–117. Bibcode:2009Natur.460..113B. doi:10.1038/nature08191. PMID 19571884. S2CID 801804.
  12. Quaranta R, Fell J, Rühle F, Rao J, Piccini I, Araúzo-Bravo MJ, et al. (January 2018). "Revised roles of ISL1 in a hES cell-based model of human heart chamber specification". eLife. 7. doi:10.7554/eLife.31706. PMC 5770158. PMID 29337667.
  13. Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, et al. (May 2012). "Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart". Circulation Research. 110 (10): 1303–1310. doi:10.1161/CIRCRESAHA.111.259630. PMC 5559221. PMID 22427341.
  14. 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". Circulation Research. 110 (7): 922–926. doi:10.1161/CIRCRESAHA.112.266510. PMC 3355870. PMID 22394517.
  15. Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, et al. (June 2011). "Distinction between two populations of islet-1-positive cells in hearts of different murine strains". Stem Cells and Development. 20 (6): 1043–1052. doi:10.1089/scd.2010.0374. PMC 5880329. PMID 20942609.

Further reading

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