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Gene Review

Isl1  -  ISL1 transcription factor, LIM/homeodomain

Mus musculus

Synonyms: Insulin gene enhancer protein ISL-1, Islet 1, Islet-1
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Disease relevance of Isl1


High impact information on Isl1

  • In these embryos, expression of Isl1 and Atoh5, essential regulators of pancreatic morphogenesis and differentiation, was severely reduced [6].
  • Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation [7].
  • A population of interneurons that express Engrailed1 (EN1), however, also fails to differentiate in Isl1 mutant embryos [7].
  • Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo [8].
  • 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 [9].

Biological context of Isl1

  • We found that Isl1-beta is a relatively more potent transcriptional activator of the insulin promoter than Isl1-alpha and that the Isl1-alpha isoform undergoes phosphorylation [1].
  • Therefore, the transcriptional activity of Isl1 is potentially regulated by the alternative splicing of its mRNA and by phosphorylation [1].
  • Maternal supplementation of RA rescues early dorsal pancreas development and restores endodermal Pdx 1 and mesenchymal Isl 1 expression as well as endocrine cell differentiation [10].
  • Our data indicate that Isl1 is a specific marker for a subset of pacemaker cells at developmental stages examined, and suggest genetic heterogeneity within the central conduction system and coronary smooth muscle [11].
  • These genetic cell-based systems should allow the direct identification of signalling pathways which guide formation, renewal and diversification of Isl1(+) cardiogenic progenitors into distinct heart cell lineages, and would complement in vitro studies in the mouse embryo during cardiac development [12].

Anatomical context of Isl1


Associations of Isl1 with chemical compounds

  • We do not however find any expression of the late-stage genes (Pax4, Pax6, Isl-1, and MafA) related to beta-cell development, and the cells do not secrete insulin upon the glucose challenge [17].
  • 4) Islet cAMP levels paralleled insulin secretion; in the presence of IBMX, but not glucose alone, cAMP was increased 2-fold more in alpha s+ vs. control islets [18].
  • BACKGROUND: Islet transplantation studies with diabetic rodents frequently use treatment with diabetogens such as alloxan or streptozotocin to render hosts hyperglycemic [19].
  • Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival [20].
  • (6) Islet-activating protein and 3-quinuclidinyl benzilate, two inhibitors of the zona pellucida-induced acrosome reaction, prevent sperm bound to ZP3-beads from undergoing the acrosome reaction [21].

Regulatory relationships of Isl1


Other interactions of Isl1

  • To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification [14].
  • 5. Most of the Pax6-, Isl1-, or PDX-1-positive cells showed co-expression of HNF-1alpha [26].
  • First, duct cells proliferated in the perfused segment, then cells co-expressing multiple islet hormones and transcription factors such as PDX-1, Nkx2.2, Isl1, and Pax6 were observed in duct cells, and newly formed islet-like cell clusters (ICCs) containing beta cells were recognized [27].
  • To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+ [28].
  • In the developing brain, almost 100% of VMH cells that contain immunoreactive ERalpha also contain Isl-1 [29].

Analytical, diagnostic and therapeutic context of Isl1


  1. Isolation and characterization of an alternatively spliced variant of transcription factor Islet-1. Ando, K., Shioda, S., Handa, H., Kataoka, K. J. Mol. Endocrinol. (2003) [Pubmed]
  2. Changes in expression of fibroblast growth factor receptors during development of the mouse retinofugal pathway. Lin, L., Taylor, J.S., Chan, S.O. J. Comp. Neurol. (2002) [Pubmed]
  3. A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyeloablative conditioning therapy. Lee, B.W., Lee, J.I., Oh, S.H., Ahn, Y.R., Chae, H.Y., Lee, M.S., Lee, M.K., Kim, K.W. Transplant. Proc. (2005) [Pubmed]
  4. Relative hypoglycemia and hyperinsulinemia in mice with heterozygous lipoprotein lipase (LPL) deficiency. Islet LPL regulates insulin secretion. Marshall, B.A., Tordjman, K., Host, H.H., Ensor, N.J., Kwon, G., Marshall, C.A., Coleman, T., McDaniel, M.L., Semenkovich, C.F. J. Biol. Chem. (1999) [Pubmed]
  5. Development of a novel beta-cell specific promoter system for the identification of insulin-producing cells in in vitro cell cultures. Fukazawa, T., Matsuoka, J., Naomoto, Y., Nakai, T., Durbin, M.L., Kojima, I., Lakey, J.R., Tanaka, N. Exp. Cell Res. (2006) [Pubmed]
  6. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Kim, S.K., Selleri, L., Lee, J.S., Zhang, A.Y., Gu, X., Jacobs, Y., Cleary, M.L. Nat. Genet. (2002) [Pubmed]
  7. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Pfaff, S.L., Mendelsohn, M., Stewart, C.L., Edlund, T., Jessell, T.M. Cell (1996) [Pubmed]
  8. Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Ericson, J., Muhr, J., Placzek, M., Lints, T., Jessell, T.M., Edlund, T. Cell (1995) [Pubmed]
  9. 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. Karlsson, O., Thor, S., Norberg, T., Ohlsson, H., Edlund, T. Nature (1990) [Pubmed]
  10. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Martín, M., Gallego-Llamas, J., Ribes, V., Kedinger, M., Niederreither, K., Chambon, P., Dollé, P., Gradwohl, G. Dev. Biol. (2005) [Pubmed]
  11. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Sun, Y., Liang, X., Najafi, N., Cass, M., Lin, L., Cai, C.L., Chen, J., Evans, S.M. Dev. Biol. (2007) [Pubmed]
  12. Cardiovascular development: towards biomedical applicability : Biology of Isl1 (+) cardiac progenitor cells in development and disease. Moretti, A., Lam, J., Evans, S.M., Laugwitz, K.L. Cell. Mol. Life Sci. (2007) [Pubmed]
  13. A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Thaler, J.P., Koo, S.J., Kania, A., Lettieri, K., Andrews, S., Cox, C., Jessell, T.M., Pfaff, S.L. Neuron (2004) [Pubmed]
  14. Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Lee, S.K., Pfaff, S.L. Neuron (2003) [Pubmed]
  15. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Eberhardt, M., Salmon, P., von Mach, M.A., Hengstler, J.G., Brulport, M., Linscheid, P., Seboek, D., Oberholzer, J., Barbero, A., Martin, I., Müller, B., Trono, D., Zulewski, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  16. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Lin, L., Bu, L., Cai, C.L., Zhang, X., Evans, S. Dev. Biol. (2006) [Pubmed]
  17. High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Cao, L.Z., Tang, D.Q., Horb, M.E., Li, S.W., Yang, L.J. Diabetes (2004) [Pubmed]
  18. Constitutively active stimulatory G-protein alpha s in beta-cells of transgenic mice causes counterregulation of the increased adenosine 3',5'-monophosphate and insulin secretion. Ma, Y.H., Landis, C., Tchao, N., Wang, J., Rodd, G., Hanahan, D., Bourne, H.R., Grodsky, G.M. Endocrinology (1994) [Pubmed]
  19. New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Mathews, C.E., Langley, S.H., Leiter, E.H. Transplantation (2002) [Pubmed]
  20. Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival. Fiorina, P., Jurewicz, M., Tanaka, K., Behazin, N., Augello, A., Vergani, A., Von Adrian, U., Smith, N.R., Sayegh, M.H., Abdi, R. Diabetes (2007) [Pubmed]
  21. Interaction of mouse sperm with purified sperm receptors covalently linked to silica beads. Vazquez, M.H., Phillips, D.M., Wassarman, P.M. J. Cell. Sci. (1989) [Pubmed]
  22. Regulation of spinal motoneuron differentiation by the combined action of Sonic hedgehog and neurotrophin 3. Dutton, R., Yamada, T., Turnley, A., Bartlett, P.F., Murphy, M. Clin. Exp. Pharmacol. Physiol. (1999) [Pubmed]
  23. Expression of DM-GRASP/BEN in the developing mouse spinal cord and various epithelia. Fraboulet, S., Schmidt-Petri, T., Dhouailly, D., Pourquié, O. Mech. Dev. (2000) [Pubmed]
  24. A pentadecapeptide fragment of islet neogenesis-associated protein increases beta-cell mass and reverses diabetes in C57BL/6J mice. Rosenberg, L., Lipsett, M., Yoon, J.W., Prentki, M., Wang, R., Jun, H.S., Pittenger, G.L., Taylor-Fishwick, D., Vinik, A.I. Ann. Surg. (2004) [Pubmed]
  25. Caudal dysgenesis in Islet-1 transgenic mice. Muller, Y.L., Yueh, Y.G., Yaworsky, P.J., Salbaum, J.M., Kappen, C. FASEB J. (2003) [Pubmed]
  26. Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas. Nammo, T., Yamagata, K., Hamaoka, R., Zhu, Q., Akiyama, T.E., Gonzalez, F.J., Miyagawa, J., Matsuzawa, Y. Diabetologia (2002) [Pubmed]
  27. Beta cell neogenesis from ducts and phenotypic conversion of residual islet cells in the adult pancreas of glucose intolerant mice induced by selective alloxan perfusion. Li, M., Miyagawa, J., Yamamoto, K., Moriwaki, M., Imagawa, A., Iwahashi, H., Yamagata, K., Tochino, Y., Hanafusa, T., Matsuzawa, Y. Endocr. J. (2002) [Pubmed]
  28. Isl1Cre reveals a common Bmp pathway in heart and limb development. Yang, L., Cai, C.L., Lin, L., Qyang, Y., Chung, C., Monteiro, R.M., Mummery, C.L., Fishman, G.I., Cogen, A., Evans, S. Development (2006) [Pubmed]
  29. Differential colocalization of Islet-1 and estrogen receptor alpha in the murine preoptic area and hypothalamus during development. Davis, A.M., Seney, M.L., Walker, H.J., Tobet, S.A. Endocrinology (2004) [Pubmed]
  30. Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Passier, R., Oostwaard, D.W., Snapper, J., Kloots, J., Hassink, R.J., Kuijk, E., Roelen, B., de la Riviere, A.B., Mummery, C. Stem Cells (2005) [Pubmed]
  31. Insulin gene can be expressed in the absence of Isl-1. Dandoy-Dron, F., Deltour, L., Monthioux, E., Bucchini, D., Jami, J. Exp. Cell Res. (1993) [Pubmed]
  32. Exendin-4 treatment improves metabolic control after rat islet transplantation to athymic mice with streptozotocin-induced diabetes. Sharma, A., Sörenby, A., Wernerson, A., Efendic, S., Kumagai-Braesch, M., Tibell, A. Diabetologia (2006) [Pubmed]
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