Gene Symbol: Isl1
Description: ISL LIM homeobox 1
Alias: Isl-1, isl-1=homeobox, insulin gene enhancer protein ISL-1, ISL1 transcription factor LIM/homeodomain (islet-1), ISL1 transcription factor, LIM/homeodomain 1, isl-1 homeobox, islet-1
Species: rat
Products:     Isl1

Top Publications

  1. Karlsson O, Thor S, Norberg T, Ohlsson H, Edlund T. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature. 1990;344:879-82 pubmed
    ..If the structural homologies between Isl-1 and the C. elegans gene products reflect functional similarities, a role for Isl-1 in the development of pancreatic endocrine cells could be envisaged. ..
  2. Pfaff S, Mendelsohn M, Stewart C, Edlund T, Jessell T. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 1996;84:309-20 pubmed
    Motor neuron differentiation is accompanied by the expression of a LIM homeodomain transcription factor, Islet1 (ISL1)...
  3. Stevens K, Hakonarson H, Kim C, Doevendans P, Koeleman B, Mital S, et al. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease. PLoS ONE. 2010;5:e10855 pubmed publisher
    ..ISLET1 (ISL1) is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular ..
  4. Dykes I, Tempest L, Lee S, Turner E. Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation. J Neurosci. 2011;31:9789-99 pubmed publisher
  5. Cai C, Liang X, Shi Y, Chu P, Pfaff S, Chen J, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5:877-89 pubmed
    Hearts of mice lacking Isl1, a LIM homeodomain transcription factor, are completely missing the outflow tract, right ventricle, and much of the atria...
  6. Ahlgren U, Pfaff S, Jessell T, Edlund T, Edlund H. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature. 1997;385:257-60 pubmed
    ..The LIM homeodomain protein ISL1 is expressed in all classes of islet cells in the adult and its expression in the embryo is initiated soon after ..
  7. Bu L, Jiang X, Martin Puig S, Caron L, Zhu S, Shao Y, et al. Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature. 2009;460:113-7 pubmed publisher
    ..Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages...
  8. Pan L, Deng M, Xie X, Gan L. ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells. Development. 2008;135:1981-90 pubmed publisher
    ..Here, we show that ISL1, a LIM-HD protein, is co-expressed with BRN3B, a POU-HD factor, in nascent post-mitotic retinal ganglion cells (..
  9. Barat Houari M, Clement K, Vatin V, Dina C, Bonhomme G, Vasseur F, et al. Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on chromosome 5q11-q13 in a French morbidly obese population suggests indication for association with type 2 diabetes. Diabetes. 2002;51:1640-3 pubmed
    ..By mutation screening of 72 obese subjects, we identified three single-nucleotide polymorphisms (SNPs) in the Isl1 gene. The allele frequencies in the morbidly obese group did not differ from that of the control group...

More Information


  1. Hao Z, Yeung J, Wolf L, Doucette R, Nazarali A. Differential expression of Hoxa-2 protein along the dorsal-ventral axis of the developing and adult mouse spinal cord. Dev Dyn. 1999;216:201-17 pubmed dyn 1999;216:201-217. ..
  2. Ando K, Shioda S, Handa H, Kataoka K. Isolation and characterization of an alternatively spliced variant of transcription factor Islet-1. J Mol Endocrinol. 2003;31:419-25 pubmed
    The LIM homeodomain protein Islet-1 (Isl1), one of the earliest markers for motor neuron differentiation, is also expressed in all classes of islet cells in the pancreas...
  3. Hol E, Schwaiger F, Werner A, Schmitt A, Raivich G, Kreutzberg G. Regulation of the LIM-type homeobox gene islet-1 during neuronal regeneration. Neuroscience. 1999;88:917-25 pubmed
    ..Moreover, in the adult nervous system islet-1 might be one of the transcription factors regulating the expression of proteins significant for the physiological intact neuronal phenotype. ..
  4. Kwon C, Qian L, Cheng P, Nigam V, Arnold J, Srivastava D. A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nat Cell Biol. 2009;11:951-7 pubmed publisher
    ..Notch1 positively, and beta-catenin negatively, regulated expression of the cardiac transcription factors, Isl1, Myocd and Smyd1...
  5. Kojima H, Nakamura T, Fujita Y, Kishi A, Fujimiya M, Yamada S, et al. Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes. 2002;51:1398-408 pubmed
    ..In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1. ..
  6. Elshatory Y, Gan L. The LIM-homeobox gene Islet-1 is required for the development of restricted forebrain cholinergic neurons. J Neurosci. 2008;28:3291-7 pubmed publisher
    ..We tested the role of the LIM-homeobox gene Isl1 in the development of forebrain cholinergic neurons by conditionally deleting Isl1 using a Six3-cre transgene...
  7. Mitsiadis T, Angeli I, James C, Lendahl U, Sharpe P. Role of Islet1 in the patterning of murine dentition. Development. 2003;130:4451-60 pubmed
    ..The LIM homeodomain protein Islet1 (ISL1) is involved in the regulation of differentiation of many cell types and organs...
  8. Sullivan K, Burns L, Black L. An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential. J Mol Cell Cardiol. 2015;88:91-100 pubmed publisher
    ..Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery. ..
  9. Huang Z, Young Seok H, Zhou B, Chen J, Chen J, Tao Y, et al. CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy. Circ Res. 2012;110:818-30 pubmed publisher
    ..Here, we report the identification, characterization, and functional examination of a novel cardiac Isl1-interacting protein (CIP)...
  10. Vincent S, Mayeuf Louchart A, Watanabe Y, Brzezinski J, Miyagawa Tomita S, Kelly R, et al. Prdm1 functions in the mesoderm of the second heart field, where it interacts genetically with Tbx1, during outflow tract morphogenesis in the mouse embryo. Hum Mol Genet. 2014;23:5087-101 pubmed publisher
    ..Our results identify PRDM1 as a potential modifier of phenotypic severity in TBX1 haploinsufficient DiGeorge syndrome patients. ..
  11. Sumazaki R, Shiojiri N, Isoyama S, Masu M, Keino Masu K, Osawa M, et al. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet. 2004;36:83-7 pubmed
    ..Thus, biliary epithelium has the potential for pancreatic differentiation and Hes1 determines biliary organogenesis by preventing the pancreatic differentiation program, probably by directly repressing transcription of Neurog3. ..
  12. Barzelay A, Hochhauser E, Entin Meer M, Chepurko Y, Birk E, Afek A, et al. Islet-1 gene delivery improves myocardial performance after experimental infarction. Atherosclerosis. 2012;223:284-90 pubmed publisher
    The LIM-homeobox transcription factor Isl1 plays a crucial role during heart embryogenesis and later on gives rise to adult resident cardiac stem cells. In this study, we aimed to discover new extra cardiac populations of Isl1 stem cells...
  13. Brønnum H, Andersen D, Schneider M, Nossent A, Nielsen S, Sheikh S. Islet-1 is a dual regulator of fibrogenic epithelial-to-mesenchymal transition in epicardial mesothelial cells. Exp Cell Res. 2013;319:424-35 pubmed publisher
    ..Islet-1 (Isl1) is a widely applied marker of progenitor cells, including the epicardial mesothelial cells (EMCs)...
  14. Zhang H, Wang W, Guo T, Yang J, Chen P, Ma K, et al. The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2. J Mol Biol. 2009;392:566-77 pubmed publisher
    The LIM-homeodomain transcription factor ISL1 (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development. Mutations in ISL1 are associated with maturity-onset diabetes of the young and type 2 diabetes...
  15. Wang M, Drucker D. The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription. J Biol Chem. 1995;270:12646-52 pubmed
    The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification...
  16. Hao A, Novotny Diermayr V, Bian W, Lin B, Lim C, Jing N, et al. The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities. Mol Biol Cell. 2005;16:1569-83 pubmed
    Islet1 (Isl1) belongs to the LIM homeodomain transcription factor family. Its roles in differentiation of motor neurons and organogenesis of pancreas and heart have been revealed...
  17. Lee S, Cuvillier J, Lee B, Shen R, Lee J, Lee S. Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs. Proc Natl Acad Sci U S A. 2012;109:3383-8 pubmed publisher
    ..The LIM complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos...
  18. Li R, Wu F, Ruonala R, Sapkota D, Hu Z, Mu X. Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PLoS ONE. 2014;9:e92105 pubmed publisher
    ..The mechanisms by which these factors collaborate are largely not known. We have shown previously that Isl1, a Lim-Homeodomain transcription factor, and Pou4f2, a class IV POU domain transcription factor, co-regulate a set ..
  19. Behravan G, Lycksell P, Larsson G. Expression, purification and characterization of the homeodomain of rat ISL-1 protein. Protein Eng. 1997;10:1327-31 pubmed
    ..A stabilization of the secondary structure was observed upon DNA binding. The free energy of unfolding at 23 degrees C was 7 kJ mol(-1) in absence of DNA and 29 kJ mol(-1) in the presence of DNA. ..
  20. Takuma N, Sheng H, Furuta Y, Ward J, Sharma K, Hogan B, et al. Formation of Rathke's pouch requires dual induction from the diencephalon. Development. 1998;125:4835-40 pubmed
    ..This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon. ..
  21. Mak K, Kronenberg H, Chuang P, Mackem S, Yang Y. Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development. 2008;135:1947-56 pubmed publisher
    ..In addition, we found that bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. ..
  22. Rogelius N, Hebsgaard J, Lundberg C, Parmar M. Reprogramming of neonatal SVZ progenitors by islet-1 and neurogenin-2. Mol Cell Neurosci. 2008;38:453-9 pubmed publisher
    ..When located in the striatum, the reprogrammed cells displayed neuroblast-like morphology. Once removed from the striatal parenchyma and allowed to further differentiation in vitro they developed into beta-III-tubulin positive neurons. ..
  23. Zhou T, Xu H, Qin Y, Lei F, Huang W, Drummen G. LIM homeobox transcription factor 1B is associated with pro-fibrotic components and apoptosis in hypoxia/reoxygenation renal tubular epithelial cells. Apoptosis. 2014;19:594-602 pubmed publisher
    ..Consequently, overexpression of LMX1B was associated with reduced cell apoptosis, whilst downregulation of LMX1B was associated with increased cell apoptosis in H-R RTEC. ..
  24. Wang M, Drucker D. 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. 1994;134:1416-22 pubmed
    ..These experiments suggest that the biological importance of isl-1 may not be restricted to neuroendocrine cell lineages and raise the possibility that isl-1 function may be regulated by sequestration in distinct cellular compartments. ..
  25. Sun Y, Dykes I, Liang X, Eng S, Evans S, Turner E. A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci. 2008;11:1283-93 pubmed publisher
    ..From E12.5 onward, however, Isl1 mutant embryos showed a loss of the nociceptive markers TrkA and Runx1 and a near absence of cutaneous innervation...
  26. Jurata L, Gill G. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol. 1997;17:5688-98 pubmed
    ..Thus, NLI may regulate the transcriptional activity of LIM homeodomain proteins by determining specific partner interactions. ..
  27. Peng S, Wang W, Meng J, Li T, Zhang H, Li Y, et al. ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells. Biochim Biophys Acta. 2005;1731:154-9 pubmed
    b>ISL1 is a LIM homeodomain protein that plays an important role in insulin gene transcriptional activation and islet cell formation...
  28. Song M, Sun Y, Bryson A, Gill G, Evans S, Pfaff S. Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity. Development. 2009;136:2923-32 pubmed publisher
    ..Here we examined how the dosage of LIM homeodomain proteins Isl1 and Isl2 and LIM-only protein Lmo4 influences the assembly and function of complexes involved in the generation of ..
  29. Holm P, Rydlander B, Luthman H, Kockum I. Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families. Diabetes. 2004;53:1584-91 pubmed
    We have previously reported suggestive linkage to chromosome 5p13-q13 in type 1 diabetic families. ISL1, a transcription factor involved in pancreas development, maps to this region...
  30. Thaler J, Koo S, Kania A, Lettieri K, Andrews S, Cox C, et al. A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Neuron. 2004;41:337-50 pubmed
    ..All spinal motor neuron subtypes initially express both Isl1 and Isl2, but Isl2 is rapidly downregulated by visceral motor neurons...
  31. Zhang L, Wahlin K, Li Y, Masuda T, Yang Z, Zack D, et al. RIT2, a neuron-specific small guanosine triphosphatase, is expressed in retinal neuronal cells and its promoter is modulated by the POU4 transcription factors. Mol Vis. 2013;19:1371-86 pubmed
    ..with expression vectors demonstrated that POU4 proteins can indeed modulate the human RIT2 promoter, and that ISL1, a LIM homeodomain factor, can further modulate the activity of the POU4 factors...
  32. Yu Z, Kong J, Pan B, Sun H, Lv T, Zhu J, et al. Islet-1 may function as an assistant factor for histone acetylation and regulation of cardiac development-related transcription factor Mef2c expression. PLoS ONE. 2013;8:e77690 pubmed publisher
    ..These data suggested that Islet-1 might function as an assistant factor that was involved in the regulation of histone acetylation and Mef2c expression via assisting p300 on specifically targeting the promoter of Mef2c. ..
  33. Liu J, Chen D, Meng X. [Discovery of rat Islet-1 gene variant and its expression in NSC]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007;23:495-7 pubmed
    ..The rat Islet-1 recombinant retroviral vector has been successfully prepared, which can be used to study the function of Islet-1 gene in NSC differentiation into cholinergic neurons. ..
  34. Lin L, Bu L, Cai C, Zhang X, Evans S. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Dev Biol. 2006;295:756-63 pubmed
    The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in both foregut endoderm and cardiogenic mesoderm and is required for earliest stages of heart development. Here, we report that isl1 is also required upstream of Shh...
  35. Gay F, Anglade I, Gong Z, Salbert G. The LIM/homeodomain protein islet-1 modulates estrogen receptor functions. Mol Endocrinol. 2000;14:1627-48 pubmed
    ..Among LIM/HD proteins, Islet-1 (ISL1) is the earliest known marker of motoneuron differentiation and has been extensively studied in this context...
  36. Granger A, Bleux C, Kottler M, Rhodes S, Counis R, Laverrière J. The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter. Mol Endocrinol. 2006;20:2093-108 pubmed
    ..Collectively, these data suggest the occurrence of a specific LIM-HD pituitary code and designate the GnRH-R gene as the first identified transcriptional target of Isl-1 in the anterior pituitary. ..
  37. Lin L, Cui L, Zhou W, Dufort D, Zhang X, Cai C, et al. Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proc Natl Acad Sci U S A. 2007;104:9313-8 pubmed
    Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart ..