Gene Symbol: isl2a
Description: ISL LIM homeobox 2a
Alias: ISL-2, isl2, wu:fc29g02, zfIsl-2, insulin gene enhancer protein isl-2a, insulin gene enhancer protein isl-2, islet-2, islet-2A, islet2, islet2a
Species: zebrafish
Products:     isl2a

Top Publications

  1. Cornell R, Eisen J. Delta signaling mediates segregation of neural crest and spinal sensory neurons from zebrafish lateral neural plate. Development. 2000;127:2873-82 pubmed
    ..Cranial neural crest derivatives are also present in deltaA mutants, revealing a genetic difference in regulation of trunk and cranial neural crest development. ..
  2. Gong Z, Hui C, Hew C. Presence of isl-1-related LIM domain homeobox genes in teleost and their similar patterns of expression in brain and spinal cord. J Biol Chem. 1995;270:3335-45 pubmed
    ..Based on these observations, we speculate that the three structurally related isl genes may play similar roles in cell determination and differentiation in the developing nervous system...
  3. Cheesman S, Layden M, Von Ohlen T, Doe C, Eisen J. Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate motoneuron formation. Development. 2004;131:5221-32 pubmed
    ..Overexpression of fish or fly Nkx6 is sufficient to generate supernumerary motoneurons in both zebrafish and flies. These results suggest that one ancestral function of Nkx6 proteins was to promote motoneuron development. ..
  4. Lewis K, Eisen J. Paraxial mesoderm specifies zebrafish primary motoneuron subtype identity. Development. 2004;131:891-902 pubmed
    ..Our findings suggest that in the absence of signals from paraxial mesoderm, primary motoneurons have a hybrid identity with respect to gene expression, and that under these conditions the CaP axon trajectory may be dominant. ..
  5. Sato Maeda M, Obinata M, Shoji W. Position fine-tuning of caudal primary motoneurons in the zebrafish spinal cord. Development. 2008;135:323-32 pubmed
    ..Results suggest that Semaphorin-Neuropilin signaling plays an important role in position fine-tuning of CaP cell bodies to ensure proper exit points of motor axons. ..
  6. Tallafuss A, Eisen J. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter. Neural Dev. 2008;3:18 pubmed publisher
  7. Hutchinson S, Eisen J. Islet1 and Islet2 have equivalent abilities to promote motoneuron formation and to specify motoneuron subtype identity. Development. 2006;133:2137-47 pubmed
    The expression of LIM homeobox genes islet1 and islet2 is tightly regulated during development of zebrafish primary motoneurons. All primary motoneurons express islet1 around the time they exit the cell cycle...
  8. Hale L, Fowler D, Eisen J. Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets. PLoS ONE. 2011;6:e25841 pubmed publisher
    ..The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation. ..
  9. Beattie C, Melancon E, Eisen J. Mutations in the stumpy gene reveal intermediate targets for zebrafish motor axons. Development. 2000;127:2653-62 pubmed
    ..These results reveal a series of intermediate targets involved in motor axon guidance and suggest that stumpy function is required for motor axons to progress from proximally located intermediate targets to distally located ones. ..

More Information


  1. Panzer J, Gibbs S, Dosch R, Wagner D, Mullins M, Granato M, et al. Neuromuscular synaptogenesis in wild-type and mutant zebrafish. Dev Biol. 2005;285:340-57 pubmed
    ..Identification of the underlying genetic defects in these mutants will extend our understanding of the cellular and molecular mechanisms that underlie the formation and function of neuromuscular and other synapses. ..
  2. Shin J, Poling J, Park H, Appel B. Notch signaling regulates neural precursor allocation and binary neuronal fate decisions in zebrafish. Development. 2007;134:1911-20 pubmed
  3. Batista M, Jacobstein J, Lewis K. Zebrafish V2 cells develop into excitatory CiD and Notch signalling dependent inhibitory VeLD interneurons. Dev Biol. 2008;322:263-75 pubmed publisher
    ..In addition, we demonstrate that Notch signalling is required for V2 cells to develop into V2b cells. In the absence of Notch signalling, all V2b cells develop as V2a cells. ..
  4. Pineda R, Svoboda K, Wright M, Taylor A, Novak A, Gamse J, et al. Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development. Development. 2006;133:3827-36 pubmed
    ..Mosaic analysis indicated that effects on ventrally projecting secondary motoneurons were non cell-autonomous. Thus, voltage-gated Na+ channels play cell-autonomous and non cell-autonomous roles during neuronal development. ..
  5. Schweitzer J, Becker T, Lefebvre J, Granato M, Schachner M, Becker C. Tenascin-C is involved in motor axon outgrowth in the trunk of developing zebrafish. Dev Dyn. 2005;234:550-66 pubmed
    ..We conclude that tenascin-C is part of a specialized extracellular matrix in the region of the horizontal myoseptum that influences the growth of motor axons. ..
  6. Hutchinson S, Cheesman S, Hale L, Boone J, Eisen J. Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression. Development. 2007;134:1671-7 pubmed
    ..We suggest that Nkx6 proteins regulate MiP development at least in part by maintaining the islet1 expression that is required both to promote the MiP subtype and to suppress interneuron development. ..
  7. Rodriguez Aznar E, Barrallo Gimeno A, Nieto M. Scratch2 prevents cell cycle re-entry by repressing miR-25 in postmitotic primary neurons. J Neurosci. 2013;33:5095-105 pubmed publisher
    ..Thus, Scratch2 appears to safeguard the homeostasis of postmitotic primary neurons by preventing cell cycle re-entry. ..
  8. Ungos J, Karlstrom R, Raible D. Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons. Development. 2003;130:5351-62 pubmed
    ..These results suggest that Hh signaling may normally promote DRG development by regulating expression of ngn1 in DRG precursors. ..
  9. Lamont R, Wu C, Ryu J, Vu W, Davari P, Sobering R, et al. The LIM-homeodomain transcription factor Islet2a promotes angioblast migration. Dev Biol. 2016;414:181-92 pubmed publisher
    ..Here, we show the Lim homeodomain transcription factor islet2a (isl2a) is expressed in the lateral posterior mesoderm prior to angioblast migration...
  10. Filippi A, Tiso N, Deflorian G, Zecchin E, Bortolussi M, Argenton F. The basic helix-loop-helix olig3 establishes the neural plate boundary of the trunk and is necessary for development of the dorsal spinal cord. Proc Natl Acad Sci U S A. 2005;102:4377-82 pubmed
    ..Thus, a proper regulation of the olig gene family is essential for the formation of three cell types (oligodendrocytes, astrocytes, and neural crest) that are unique to vertebrates. ..
  11. Glinka M, Herrmann T, Funk N, Havlicek S, Rossoll W, Winkler C, et al. The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons. Hum Mol Genet. 2010;19:1951-66 pubmed publisher
    ..Our data suggest that hnRNP-R-mediated axonal beta-actin mRNA translocation plays an essential physiological role for axon growth and presynaptic differentiation. ..
  12. Luo N, Li H, Xiang B, Qiao L, He J, Ji Y, et al. Syndecan-4 modulates the proliferation of neural cells and the formation of CaP axons during zebrafish embryonic neurogenesis. Sci Rep. 2016;6:25300 pubmed publisher
    ..Collectively, these data indicate that Syn4 suppresses the cellular proliferation during neurogenesis and is crucial for the formation of CaP axons during zebrafish embryogenesis. ..
  13. Gong J, Wang X, Zhu C, Dong X, Zhang Q, Wang X, et al. Insm1a Regulates Motor Neuron Development in Zebrafish. Front Mol Neurosci. 2017;10:274 pubmed publisher
    ..Taken together, these data indicated that insm1a regulated the motor neuron development, at least in part, through modulation of the expressions of olig2 and nkx6.1. ..
  14. Beattie C, Hatta K, Halpern M, Liu H, Eisen J, Kimmel C. Temporal separation in the specification of primary and secondary motoneurons in zebrafish. Dev Biol. 1997;187:171-82 pubmed
    ..These results suggest that both primary and secondary motoneurons are specified by signals from midline tissues, but at very different stages of embryonic development. ..
  15. Liedtke D, Winkler C. Midkine-b regulates cell specification at the neural plate border in zebrafish. Dev Dyn. 2008;237:62-74 pubmed
    ..Our results imply that Mdkb is required for the earliest steps of cell specification at the neural plate border in zebrafish...
  16. Aoki M, Segawa H, Naito M, Okamoto H. Identification of possible downstream genes required for the extension of peripheral axons in primary sensory neurons. Biochem Biophys Res Commun. 2014;445:357-62 pubmed publisher
    The LIM-homeodomain transcription factor Islet2a establishes neuronal identity in the developing nervous system...
  17. Coppola E, D Autréaux F, Nomaksteinsky M, Brunet J. Phox2b expression in the taste centers of fish. J Comp Neurol. 2012;520:3633-49 pubmed publisher
  18. Song Y, Selak M, Watson C, Coutts C, Scherer P, Panzer J, et al. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD). PLoS ONE. 2009;4:e8329 pubmed publisher
    ..These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention. ..
  19. Yeh C, Kao S, Cheng Y, Hsu L. Knockdown of cyclin-dependent kinase 10 (cdk10) gene impairs neural progenitor survival via modulation of raf1a gene expression. J Biol Chem. 2013;288:27927-39 pubmed publisher
    ..This result is similar to that demonstrated by decreased islet2 expression in the dorsal regions...
  20. Tanaka H, Maeda R, Shoji W, Wada H, Masai I, Shiraki T, et al. Novel mutations affecting axon guidance in zebrafish and a role for plexin signalling in the guidance of trigeminal and facial nerve axons. Development. 2007;134:3259-69 pubmed
  21. Zhang T, Zhou X, Ma X, Liu J. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos. Aquat Toxicol. 2015;167:68-76 pubmed publisher
    ..Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. ..
  22. Irimia M, Tena J, Alexis M, Fernández Miñán A, Maeso I, Bogdanovic O, et al. Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints. Genome Res. 2012;22:2356-67 pubmed publisher
  23. Latimer A, Jessen J. Hgf/c-met expression and functional analysis during zebrafish embryogenesis. Dev Dyn. 2008;237:3904-15 pubmed publisher
    ..Later, c-met is expressed in kidney, islet2-positive neurons, and liver...
  24. Kim S, Kim S, Kim H, Chung A, Cha Y, Kim C, et al. Frizzled 8a function is required for oligodendrocyte development in the zebrafish spinal cord. Dev Dyn. 2008;237:3324-31 pubmed publisher
    ..In addition, we demonstrate that Wnt signaling activation after the specification of OPCs blocks the formation of mature oligodendrocytes and results in the elimination of OPCs. ..
  25. Tamme R, Wells S, Conran J, Lardelli M. The identity and distribution of neural cells expressing the mesodermal determinant spadetail. BMC Dev Biol. 2002;2:9 pubmed
  26. Feldner J, Becker T, Goishi K, Schweitzer J, Lee P, Schachner M, et al. Neuropilin-1a is involved in trunk motor axon outgrowth in embryonic zebrafish. Dev Dyn. 2005;234:535-49 pubmed
    ..Thus, neuropilin-1a in primary motor neurons may integrate signals from several ligands and is needed for proper segmental growth of primary motor nerves in zebrafish. ..
  27. Mich J, Chen J. Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish. Development. 2011;138:5113-9 pubmed publisher
    ..We also provide evidence that RA pathway activation can modulate Gli function in a Hh ligand-independent manner. These findings support a model in which Hh and RA signaling cooperate to promote PMN cell fates in zebrafish. ..
  28. Schafer M, Kinzel D, Winkler C. Discontinuous organization and specification of the lateral floor plate in zebrafish. Dev Biol. 2007;301:117-29 pubmed
    ..We conclude that different levels of HH and Nkx2.2 activities are responsible for the alternating appearance of LFP and p3 neuronal progenitor cells in the zebrafish ventral neural tube. ..
  29. Takamiya M, Campos Ortega J. Hedgehog signalling controls zebrafish neural keel morphogenesis via its level-dependent effects on neurogenesis. Dev Dyn. 2006;235:978-97 pubmed
    ..Such differences seem to be created in part by regional effector signalling; the effects of high Hh-signalling on medial neurogenesis can be reversed in accordance to medial Tri/Stbm level, in a polarity independent manner. ..
  30. Yin W, Hu B. Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish. Exp Neurol. 2014;251:72-83 pubmed publisher
    ..These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development. ..
  31. Wilfinger A, Arkhipova V, Meyer D. Cell type and tissue specific function of islet genes in zebrafish pancreas development. Dev Biol. 2013;378:25-37 pubmed publisher
    ..We find that isl1 expression in the pancreatic mesenchyme overlaps with that of the related genes isl2a and isl2b and that pancreatic expression of isl-genes is independent of each other...
  32. Zhang J, Granato M. The zebrafish unplugged gene controls motor axon pathway selection. Development. 2000;127:2099-111 pubmed
    ..These data suggest that unplugged defines a somite-derived signal that elicits differential guidance decisions in motor growth cones. ..
  33. Cretekos C, Grunwald D. alyron, an insertional mutation affecting early neural crest development in zebrafish. Dev Biol. 1999;210:322-38 pubmed
  34. Park H, Boyce J, Shin J, Appel B. Oligodendrocyte specification in zebrafish requires notch-regulated cyclin-dependent kinase inhibitor function. J Neurosci. 2005;25:6836-44 pubmed
  35. Jurynec M, Xia R, Mackrill J, Gunther D, Crawford T, Flanigan K, et al. Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci U S A. 2008;105:12485-90 pubmed publisher
  36. Seredick S, Van Ryswyk L, Hutchinson S, Eisen J. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics. Neural Dev. 2012;7:35 pubmed publisher
    ..This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons. ..
  37. Chittenden T, Claes F, Lanahan A, Autiero M, Palac R, Tkachenko E, et al. Selective regulation of arterial branching morphogenesis by synectin. Dev Cell. 2006;10:783-95 pubmed
    ..We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process. ..
  38. Ohata S, Kinoshita S, Aoki R, Tanaka H, Wada H, Tsuruoka Kinoshita S, et al. Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain. Development. 2009;136:1653-63 pubmed publisher
    ..Together, these findings suggest that fucosylated glycans expressed in neuroepithelial cells are required to guide the migration of vagus motor neuron progenitors. ..
  39. Won M, Ro H, Park H, Kim K, Huh T, Kim C, et al. Dynamic expression patterns of zebrafish 1G5 (1G5z), a calmodulin kinase-like gene in the developing nervous system. Dev Dyn. 2006;235:835-42 pubmed
    ..In addition, bromodeoxyuridine staining further confirmed that the 1G5z-positive cells were postmitotic sensory and interneurons. ..
  40. Morimura R, Nozawa K, Tanaka H, Ohshima T. Phosphorylation of Dpsyl2 (CRMP2) and Dpsyl3 (CRMP4) is required for positioning of caudal primary motor neurons in the zebrafish spinal cord. Dev Neurobiol. 2013;73:911-20 pubmed publisher
    ..These results suggest that the phosphorylation of Dpysl2 and Dpysl3 by Cdk5 and Dyrk2 is required for correct positioning of CaP motor neurons in the zebrafish spinal cord. ..
  41. Miyashita T, Yeo S, Hirate Y, Segawa H, Wada H, Little M, et al. PlexinA4 is necessary as a downstream target of Islet2 to mediate Slit signaling for promotion of sensory axon branching. Development. 2004;131:3705-15 pubmed
    ..The reason why different neurons respond to Slit in different ways is largely unknown. Islet2 is a LIM/homeodomain-type transcription factor that specifically regulates elongation and branching of the ..
  42. Tanaka H, Nojima Y, Shoji W, Sato M, Nakayama R, Ohshima T, et al. Islet1 selectively promotes peripheral axon outgrowth in Rohon-Beard primary sensory neurons. Dev Dyn. 2011;240:9-22 pubmed publisher
    ..These data indicate that Dpysl3 is cooperating with Sema3d in the peripheral axon outgrowth, and Isl1 is required for the selective outgrowth of the peripheral axons of RB neurons by maintaining the expression of dpysl3. ..
  43. Yeo S, Chitnis A. Jagged-mediated Notch signaling maintains proliferating neural progenitors and regulates cell diversity in the ventral spinal cord. Proc Natl Acad Sci U S A. 2007;104:5913-8 pubmed
  44. An M, Henion P. The zebrafish sf3b1b460 mutant reveals differential requirements for the sf3b1 pre-mRNA processing gene during neural crest development. Int J Dev Biol. 2012;56:223-37 pubmed publisher
    ..Further, the developmental defects caused by the sf3b1(b460) mutation provide insights into genetic interactions among members of the gene regulatory network controlling neural crest development...
  45. Liu L, Lin M, Lai Z, Jiang J, Huang Y, Jao L, et al. Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway. J Biomed Sci. 2016;23:59 pubmed publisher
    ..Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems. ..
  46. Olesnicky E, Hernandez Lagunas L, Artinger K. prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons. Genesis. 2010;48:656-66 pubmed publisher
    ..In addition, we identified a number of other novel downstream targets of Prdm1a that may be important for the development of diverse tissues during zebrafish embryogenesis. ..
  47. Tiso N, Filippi A, Benato F, Negrisolo E, Modena N, Vaccari E, et al. Differential expression and regulation of olig genes in zebrafish. J Comp Neurol. 2009;515:378-96 pubmed publisher
    ..Our findings suggest a role for olig genes in CNS patterning as well as in multiple cell fate decisions during neural differentiation. ..
  48. Zeller J, Granato M. The zebrafish diwanka gene controls an early step of motor growth cone migration. Development. 1999;126:3461-72 pubmed
  49. Kawakami A, Nojima Y, Toyoda A, Takahoko M, Satoh M, Tanaka H, et al. The zebrafish-secreted matrix protein you/scube2 is implicated in long-range regulation of hedgehog signaling. Curr Biol. 2005;15:480-8 pubmed
    ..We further show that Bmp activity can be attenuated by the coexpression of Scube2. Our data support the idea that Scube2 can modulate the long-range action of Bmp-dependent signaling in the neural tube and somites. ..
  50. Bisgrove B, Raible D, Walter V, Eisen J, Grunwald D. Expression of c-ret in the zebrafish embryo: potential roles in motoneuronal development. J Neurobiol. 1997;33:749-68 pubmed
    ..primary (CaP) motoneurons and transcripts can be detected shortly before the expression of the CaP-specific gene, islet2. We suggest that c-ret may play a role in specifying CaP cell identity...
  51. Liu C, Ma W, Su W, Zhang J. Prdm14 acts upstream of islet2 transcription to regulate axon growth of primary motoneurons in zebrafish. Development. 2012;139:4591-600 pubmed publisher
    ..Mechanistically, Prdm14 protein binds to the promoter region of islet2, a known transcription factor required for CaP development...
  52. Seredick S, Hutchinson S, Van Ryswyk L, Talbot J, Eisen J. Lhx3 and Lhx4 suppress Kolmer-Agduhr interneuron characteristics within zebrafish axial motoneurons. Development. 2014;141:3900-9 pubmed publisher
    ..In conjunction with our previous work, these data reveal that distinct transcription factor families are deployed in post-mitotic MNs to unequivocally assign MN fate and suppress the development of alternative pMN-derived IN fates. ..
  53. Li T, Fan J, Blanco Sanchez B, Giagtzoglou N, Lin G, Yamamoto S, et al. Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. PLoS Genet. 2016;12:e1006054 pubmed publisher
    ..Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues. ..
  54. Witzel H, Cheedipudi S, Gao R, Stainier D, Dobreva G. Isl2b regulates anterior second heart field development in zebrafish. Sci Rep. 2017;7:41043 pubmed publisher
    ..In zebrafish, isl2a mutants show defects in cardiac looping, whereas isl2b is required for arterial pole development...
  55. Van Ryswyk L, Simonson L, Eisen J. The role of inab in axon morphology of an identified zebrafish motoneuron. PLoS ONE. 2014;9:e88631 pubmed publisher
    ..We show that inab is necessary for proper axon morphology of a specific motoneuron subtype. ..
  56. Conway G. STAT3-dependent pathfinding and control of axonal branching and target selection. Dev Biol. 2006;296:119-36 pubmed
    ..These results are consistent with and highlight a fundamental role for STAT3 as a factor promoting cellular responses to guidance cues, not only in nonneural cells but also in pathfinding neurons. ..
  57. Al Oustah A, Danesin C, Khouri Farah N, Farreny M, Escalas N, Cochard P, et al. Dynamics of sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring sulfatase 1. Development. 2014;141:1392-403 pubmed publisher
    ..Our work, by pointing out the key role of Sulf1 in regulating Shh-dependent neural cell diversity, highlights a novel level of regulation, which involves temporal evolution of Shh source properties. ..
  58. Hsu R, Yang H, Tsai H. Labeled microRNA pull-down assay system: an experimental approach for high-throughput identification of microRNA-target mRNAs. Nucleic Acids Res. 2009;37:e77 pubmed publisher
    ..elegans and zebrafish, yielding fewer false positive results than those produced by using only the bioinformatics approach. ..