isl2a

Summary

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

Top Publications

  1. ncbi Tenascin-C is involved in motor axon outgrowth in the trunk of developing zebrafish
    Jörn Schweitzer
    Zentrum für Molekulare Neurobiologie, Hamburg, Germany
    Dev Dyn 234:550-66. 2005
  2. ncbi The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter
    Alexandra Tallafuss
    Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA
    Neural Dev 3:18. 2008
  3. ncbi Position fine-tuning of caudal primary motoneurons in the zebrafish spinal cord
    Mika Sato-Maeda
    Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980 8575, Japan
    Development 135:323-32. 2008
  4. ncbi Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate motoneuron formation
    Sarah E Cheesman
    Institute of Neuroscience, 1254 University of Oregon, Eugene OR, 97403 1254, USA
    Development 131:5221-32. 2004
  5. ncbi Neuromuscular synaptogenesis in wild-type and mutant zebrafish
    Jessica A Panzer
    Department of Neuroscience, University of Pennsylvania School of Medicine, 215 Stemmler Hall, 3610 Hamilton Walk, Philadelphia, PA 19104 6074, USA
    Dev Biol 285:340-57. 2005
  6. ncbi Delta signaling mediates segregation of neural crest and spinal sensory neurons from zebrafish lateral neural plate
    R A Cornell
    Institute of Neuroscience, Eugene, Oregon 97403, USA uoregon edu
    Development 127:2873-82. 2000
  7. ncbi Islet1 and Islet2 have equivalent abilities to promote motoneuron formation and to specify motoneuron subtype identity
    Sarah A Hutchinson
    Institute of Neuroscience, University of Oregon, Eugene, 97403, USA
    Development 133:2137-47. 2006
  8. ncbi Notch signaling regulates neural precursor allocation and binary neuronal fate decisions in zebrafish
    Jimann Shin
    Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA
    Development 134:1911-20. 2007
  9. ncbi Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development
    Ricardo H Pineda
    Department of Physiology and Biophysics, 8307 University of Colorado Denver and Health Sciences Center, Aurora, CO 80045, USA
    Development 133:3827-36. 2006
  10. ncbi Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression
    Sarah A Hutchinson
    Institute of Neuroscience, 1254 University of Oregon, Eugene OR 97403, USA
    Development 134:1671-7. 2007

Research Grants

  1. Spinal Muscular Atrophy: Is it a motor axon disease?
    CHRISTINE BEATTIE; Fiscal Year: 2009
  2. Spinal Muscular Atrophy: Is it a motor axon disease?
    Christine E Beattie; Fiscal Year: 2010

Scientific Experts

  • N Tiso
  • Richard Tamme
  • CHRISTINE BEATTIE
  • Greg Conway
  • Masanari Takamiya
  • Sang Yeob Yeo
  • Alexandra Tallafuss
  • Hideomi Tanaka
  • Atsushi Kawakami
  • Judith S Eisen
  • Hae Chul Park
  • Sarah A Hutchinson
  • Laura A Hale
  • Christoph Winkler
  • Jessica A Panzer
  • Jimann Shin
  • Hae-Chul Park
  • Katharine E Lewis
  • Sarah E Cheesman
  • Jörn Schweitzer
  • Eugenia Olesnicky
  • Michael Glinka
  • Ren Jun Hsu
  • Shinya Ohata
  • Yuanquan Song
  • Michael J Jurynec
  • Andrew J Latimer
  • Manuel F Batista
  • Daniel Liedtke
  • Mika Sato-Maeda
  • Suhyun Kim
  • Cheol Hee Kim
  • Matthias Schafer
  • Rita J Balice-Gordon
  • Tae Lin Huh
  • Hitoshi Okamoto
  • Hironori Wada
  • Ricardo H Pineda
  • Bruce Appel
  • Minho Won
  • Thomas W Chittenden
  • Catherina G Becker
  • Melitta Schachner
  • Alida Filippi
  • Julia Feldner
  • Michael Granato
  • Thomas Becker
  • Toshio Miyashita
  • Josette M Ungos
  • Daniel K Fowler
  • Michael Sendtner
  • Kristin Bruk Artinger
  • Wilfried Rossoll
  • Natalja Funk
  • J Zhang
  • R A Cornell
  • Steven Havlicek
  • Laura Hernandez-Lagunas
  • Thomas Herrmann
  • Christopher Coutts
  • Ronald G Gregg
  • Huai Jen Tsai
  • Hsin Jung Yang
  • Gregory Willer
  • Paul C Scherer
  • Shigeharu Kinoshita
  • Sachiko Tsuruoka-Kinoshita
  • Ryo Aoki
  • Shugo Watabe
  • Sarah Gibbs
  • M Granato
  • Corey T Watson
  • Marion O Scott
  • Michael J Bennett
  • Takashi Tsuboi
  • Declan W Ali
  • Mary A Selak
  • Ho Kim
  • Wataru Shoji
  • C J Cretekos
  • Kevin M Flanigan
  • Ah Young Chung
  • Masuo Obinata
  • Michael T Howard
  • David Jonah Grunwald
  • Jonathan J Abramson
  • Jason R Jessen
  • John J Mackrill
  • Thomas Crawford
  • Ruohong Xia

Detail Information

Publications45

  1. ncbi Tenascin-C is involved in motor axon outgrowth in the trunk of developing zebrafish
    Jörn Schweitzer
    Zentrum für Molekulare Neurobiologie, Hamburg, Germany
    Dev Dyn 234:550-66. 2005
    ..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...
  2. ncbi The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter
    Alexandra Tallafuss
    Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA
    Neural Dev 3:18. 2008
    ..Here we test the role of Met in development of motoneurons in embryonic zebrafish...
  3. ncbi Position fine-tuning of caudal primary motoneurons in the zebrafish spinal cord
    Mika Sato-Maeda
    Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980 8575, Japan
    Development 135:323-32. 2008
    ..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...
  4. ncbi Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate motoneuron formation
    Sarah E Cheesman
    Institute of Neuroscience, 1254 University of Oregon, Eugene OR, 97403 1254, USA
    Development 131:5221-32. 2004
    ..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...
  5. ncbi Neuromuscular synaptogenesis in wild-type and mutant zebrafish
    Jessica A Panzer
    Department of Neuroscience, University of Pennsylvania School of Medicine, 215 Stemmler Hall, 3610 Hamilton Walk, Philadelphia, PA 19104 6074, USA
    Dev Biol 285:340-57. 2005
    ..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...
  6. ncbi Delta signaling mediates segregation of neural crest and spinal sensory neurons from zebrafish lateral neural plate
    R A Cornell
    Institute of Neuroscience, Eugene, Oregon 97403, USA uoregon edu
    Development 127:2873-82. 2000
    ..Cranial neural crest derivatives are also present in deltaA mutants, revealing a genetic difference in regulation of trunk and cranial neural crest development...
  7. ncbi Islet1 and Islet2 have equivalent abilities to promote motoneuron formation and to specify motoneuron subtype identity
    Sarah A Hutchinson
    Institute of Neuroscience, University of Oregon, Eugene, 97403, USA
    Development 133:2137-47. 2006
    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. ncbi Notch signaling regulates neural precursor allocation and binary neuronal fate decisions in zebrafish
    Jimann Shin
    Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA
    Development 134:1911-20. 2007
    ....
  9. ncbi Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development
    Ricardo H Pineda
    Department of Physiology and Biophysics, 8307 University of Colorado Denver and Health Sciences Center, Aurora, CO 80045, USA
    Development 133:3827-36. 2006
    ..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...
  10. ncbi Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression
    Sarah A Hutchinson
    Institute of Neuroscience, 1254 University of Oregon, Eugene OR 97403, USA
    Development 134:1671-7. 2007
    ..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...
  11. ncbi Mutations in the stumpy gene reveal intermediate targets for zebrafish motor axons
    C E Beattie
    Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA
    Development 127:2653-62. 2000
    ..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...
  12. ncbi Novel mutations affecting axon guidance in zebrafish and a role for plexin signalling in the guidance of trigeminal and facial nerve axons
    Hideomi Tanaka
    Laboratory for Developmental Gene Regulation, Brain Science Institute, The Institute of Physical and Chemical Research RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Development 134:3259-69. 2007
    ....
  13. ncbi Midkine-b regulates cell specification at the neural plate border in zebrafish
    Daniel Liedtke
    Department of Physiological Chemistry I, Biocenter, University of Wurzburg, Wurzburg, Germany
    Dev Dyn 237:62-74. 2008
    ..Our results imply that Mdkb is required for the earliest steps of cell specification at the neural plate border in zebrafish...
  14. ncbi Jagged-mediated Notch signaling maintains proliferating neural progenitors and regulates cell diversity in the ventral spinal cord
    Sang Yeob Yeo
    Department of Genetic Engineering, Kyungpook National University, 1370 san Kyuk dong, Buk Gu, Daegu 702 701, Republic of Korea
    Proc Natl Acad Sci U S A 104:5913-8. 2007
    ....
  15. ncbi Zebrafish V2 cells develop into excitatory CiD and Notch signalling dependent inhibitory VeLD interneurons
    Manuel F Batista
    Department of Physiology, Development and Neuroscience, University of Cambridge, Anatomy Building, Downing Street, Cambridge, UK
    Dev Biol 322:263-75. 2008
    ..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...
  16. ncbi Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle
    Michael J Jurynec
    Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 105:12485-90. 2008
    ....
  17. ncbi Islet1 selectively promotes peripheral axon outgrowth in Rohon-Beard primary sensory neurons
    Hideomi Tanaka
    Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute BSI, Saitama, Japan
    Dev Dyn 240:9-22. 2011
    ..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...
  18. ncbi prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons
    Eugenia Olesnicky
    Department of Craniofacial Biology, University of Colorado, Denver School of Dental Medicine, Aurora, Colorado 80045, USA
    Genesis 48:656-66. 2010
    ..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...
  19. ncbi The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons
    Michael Glinka
    Institute for Clinical Neurobiology, Zinklesweg 10, 97078 Wurzburg, Germany
    Hum Mol Genet 19:1951-66. 2010
    ..Our data suggest that hnRNP-R-mediated axonal beta-actin mRNA translocation plays an essential physiological role for axon growth and presynaptic differentiation...
  20. ncbi Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD)
    Yuanquan Song
    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 4:e8329. 2009
    ..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...
  21. ncbi Differential expression and regulation of olig genes in zebrafish
    Natascia Tiso
    Department of Biology, University of Padova, I 35131 Padova, Italy
    J Comp Neurol 515:378-96. 2009
    ..Our findings suggest a role for olig genes in CNS patterning as well as in multiple cell fate decisions during neural differentiation...
  22. ncbi Labeled microRNA pull-down assay system: an experimental approach for high-throughput identification of microRNA-target mRNAs
    Ren Jun Hsu
    Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan
    Nucleic Acids Res 37:e77. 2009
    ..elegans and zebrafish, yielding fewer false positive results than those produced by using only the bioinformatics approach...
  23. ncbi Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain
    Shinya Ohata
    Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, Saitama, Japan
    Development 136:1653-63. 2009
    ..Together, these findings suggest that fucosylated glycans expressed in neuroepithelial cells are required to guide the migration of vagus motor neuron progenitors...
  24. ncbi Hgf/c-met expression and functional analysis during zebrafish embryogenesis
    Andrew J Latimer
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Dev Dyn 237:3904-15. 2008
    ..Later, c-met is expressed in kidney, islet2-positive neurons, and liver...
  25. ncbi Frizzled 8a function is required for oligodendrocyte development in the zebrafish spinal cord
    Suhyun Kim
    Graduate School of Medicine, Korea University, Ansan, Gyeonggido, Republic of Korea
    Dev Dyn 237:3324-31. 2008
    ..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...
  26. ncbi Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets
    Laura A Hale
    Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America
    PLoS ONE 6:e25841. 2011
    ..Here we investigate the molecular basis of the signaling interaction between the intermediate target and the motoneurons...
  27. ncbi Discontinuous organization and specification of the lateral floor plate in zebrafish
    Matthias Schafer
    Department of Physiological Chemistry I, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
    Dev Biol 301:117-29. 2007
    ..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...
  28. ncbi Temporal separation in the specification of primary and secondary motoneurons in zebrafish
    C E Beattie
    Institute of Neuroscience, University of Oregon, Eugene 97401, USA
    Dev Biol 187:171-82. 1997
    ..These results suggest that both primary and secondary motoneurons are specified by signals from midline tissues, but at very different stages of embryonic development...
  29. ncbi Expression of c-ret in the zebrafish embryo: potential roles in motoneuronal development
    B W Bisgrove
    Department of Human Genetics, University of Utah, Salt Lake City 84112, USA
    J Neurobiol 33:749-68. 1997
    ..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...
  30. ncbi alyron, an insertional mutation affecting early neural crest development in zebrafish
    C J Cretekos
    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, 84112, USA
    Dev Biol 210:322-38. 1999
    ....
  31. ncbi The zebrafish diwanka gene controls an early step of motor growth cone migration
    J Zeller
    Department of Cell and Developmental Biology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 6058, USA
    Development 126:3461-72. 1999
    ....
  32. ncbi The zebrafish unplugged gene controls motor axon pathway selection
    J Zhang
    Department of Cell and Developmental Biology and Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 6058, USA
    Development 127:2099-111. 2000
    ..These data suggest that unplugged defines a somite-derived signal that elicits differential guidance decisions in motor growth cones...
  33. ncbi The identity and distribution of neural cells expressing the mesodermal determinant spadetail
    Richard Tamme
    Department of Molecular Biosciences, The University of Adelaide, Adelaide, SA 5005, Australia
    BMC Dev Biol 2:9. 2002
    ..The mechanism(s) generating the apparently irregular rostrocaudal distribution of spt-expressing cells in the developing CNS is unknown...
  34. ncbi Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons
    Josette M Ungos
    Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195 7420 USA
    Development 130:5351-62. 2003
    ..These results suggest that Hh signaling may normally promote DRG development by regulating expression of ngn1 in DRG precursors...
  35. ncbi Paraxial mesoderm specifies zebrafish primary motoneuron subtype identity
    Katharine E Lewis
    Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403, USA
    Development 131:891-902. 2004
    ..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...
  36. ncbi PlexinA4 is necessary as a downstream target of Islet2 to mediate Slit signaling for promotion of sensory axon branching
    Toshio Miyashita
    Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2 1, Hirosawa, Wako, Saitama 351 0198, Japan
    Development 131:3705-15. 2004
    ..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 ..
  37. ncbi The basic helix-loop-helix olig3 establishes the neural plate boundary of the trunk and is necessary for development of the dorsal spinal cord
    Alida Filippi
    Dipartimento di Biologia and Facolta di Psicologia, Universita degli Studi di Padova, Via Ugo Bassi 58 B, I 35121 Padua, Italy
    Proc Natl Acad Sci U S A 102:4377-82. 2005
    ..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...
  38. ncbi The zebrafish-secreted matrix protein you/scube2 is implicated in long-range regulation of hedgehog signaling
    Atsushi Kawakami
    Department of Biological Science, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Curr Biol 15:480-8. 2005
    ..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...
  39. ncbi Oligodendrocyte specification in zebrafish requires notch-regulated cyclin-dependent kinase inhibitor function
    Hae Chul Park
    Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235 1634, USA
    J Neurosci 25:6836-44. 2005
    ....
  40. ncbi Neuropilin-1a is involved in trunk motor axon outgrowth in embryonic zebrafish
    Julia Feldner
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Hamburg, Germany
    Dev Dyn 234:535-49. 2005
    ..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...
  41. ncbi Dynamic expression patterns of zebrafish 1G5 (1G5z), a calmodulin kinase-like gene in the developing nervous system
    Minho Won
    Department of Biology, School of Bioscience and Biotechnology, Chungnam National University, South Korea
    Dev Dyn 235:835-42. 2006
    ..In addition, bromodeoxyuridine staining further confirmed that the 1G5z-positive cells were postmitotic sensory and interneurons...
  42. ncbi Hedgehog signalling controls zebrafish neural keel morphogenesis via its level-dependent effects on neurogenesis
    Masanari Takamiya
    Institute of Developmental Biology, University of Cologne, Gyrhofstrasse 17, D 50923 Cologne, Germany
    Dev Dyn 235:978-97. 2006
    ..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...
  43. ncbi STAT3-dependent pathfinding and control of axonal branching and target selection
    Greg Conway
    Life Sciences Division, MS239 11, NASA Ames Research Center, Moffett Field, CA 94035, USA
    Dev Biol 296:119-36. 2006
    ..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...
  44. ncbi Selective regulation of arterial branching morphogenesis by synectin
    Thomas W Chittenden
    Angiogenesis Research Center, Section of Cardiology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Dev Cell 10:783-95. 2006
    ..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...
  45. ncbi Presence of isl-1-related LIM domain homeobox genes in teleost and their similar patterns of expression in brain and spinal cord
    Z Gong
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    J Biol Chem 270:3335-45. 1995
    ..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...

Research Grants9

  1. Spinal Muscular Atrophy: Is it a motor axon disease?
    CHRISTINE BEATTIE; Fiscal Year: 2009
    ..Experiments outlined in this proposal will directly test the hypothesis that SMA is a motor axon disease and will reveal whether SMN functions in a complex crucial for localized protein translation in motor axon growth cones. ..
  2. Spinal Muscular Atrophy: Is it a motor axon disease?
    Christine E Beattie; Fiscal Year: 2010
    ..The proposed experiments will elucidate the interaction and function of plastin 3 as it relates to SMN and has the potential to reveal novel therapeutic targets. ..