ISL1

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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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. 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.
  • Riggs AC, Tanizawa Y, Aoki M, Wasson J, Ferrer J, Rabin DU, Vaxillaire M, Froguel P, Permutt MA (1995). "Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM". Diabetes. 44 (6): 689–94. doi:10.2337/diabetes.44.6.689. PMID 7789634.
  • Wang M, Drucker DJ (1994). "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". Endocrinology. 134 (3): 1416–22. doi:10.1210/en.134.3.1416. PMID 7907017.
  • Pfaff SL, Mendelsohn M, Stewart CL, Edlund T, Jessell TM (1996). "Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation". Cell. 84 (2): 309–20. doi:10.1016/S0092-8674(00)80985-X. PMID 8565076.
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H (1997). "Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells". Nature. 385 (6613): 257–60. doi:10.1038/385257a0. PMID 9000074.
  • Jurata LW, Pfaff SL, Gill GN (1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". J. Biol. Chem. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID 9452425.
  • Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG (1999). "RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex". Nat. Genet. 22 (4): 394–9. doi:10.1038/11970. PMID 10431247.
  • Gay F, Anglade I, Gong Z, Salbert G (2001). "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.
  • Ostendorff HP, Peirano RI, Peters MA, Schlüter A, Bossenz M, Scheffner M, Bach I (2002). "Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors". Nature. 416 (6876): 99–103. doi:10.1038/416099a. PMID 11882901.
  • Holm P, Rydlander B, Luthman H, Kockum I, European Consortium for IDDM Genome Studies (2004). "Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families". Diabetes. 53 (6): 1584–91. doi:10.2337/diabetes.53.6.1584. PMID 15161765.
  • Hori Y, Gu X, Xie X, Kim SK (2006). "Differentiation of insulin-producing cells from human neural progenitor cells". PLoS Med. 2 (4): e103. doi:10.1371/journal.pmed.0020103. PMC 1087208. PMID 15839736.
  • 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 (2005). "Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development". Development. 132 (10): 2463–74. doi:10.1242/dev.01827. PMID 15843409.
  • Peng SY, Wang WP, Meng J, Li T, Zhang H, Li YM, Chen P, Ma KT, Zhou CY (2006). "ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells". Biochim. Biophys. Acta. 1731 (3): 154–9. doi:10.1016/j.bbaexp.2005.08.013. PMID 16321656.

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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