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PMID: 18369445 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Leukocyte tyrosine kinase functions in pigment cell development.

PLoS genetics ·Vol. 4 ·No. 3 ·2008-03-07 ·Pages e1000026

Lopes SS, Yang X, Müller J, Carney TJ, McAdow AR, Rauch GJ, Jacoby AS, Hurst LD, Delfino-Machín M, Haffter P, Geisler R, Johnson SL, Ward A, Kelsh RN

Abstract

A fundamental problem in developmental biology concerns how multipotent precursors choose specific fates. Neural crest cells (NCCs) are multipotent, yet the mechanisms driving specific fate choices remain incompletely understood. Sox10 is required for specification of neural cells and melanocytes from NCCs. Like sox10 mutants, zebrafish shady mutants lack iridophores; we have proposed that sox10 and shady are required for iridophore specification from NCCs. We show using diverse approaches that shady encodes zebrafish leukocyte tyrosine kinase (Ltk). Cell transplantation studies show that Ltk acts cell-autonomously within the iridophore lineage. Consistent with this, ltk is expressed in a subset of NCCs, before becoming restricted to the iridophore lineage. Marker analysis reveals a primary defect in iridophore specification in ltk mutants. We saw no evidence for a fate-shift of neural crest cells into other pigment cell fates and some NCCs were subsequently lost by apoptosis. These features are also characteristic of the neural crest cell phenotype in sox10 mutants, leading us to examine iridophores in sox10 mutants. As expected, sox10 mutants largely lacked iridophore markers at late stages. In addition, sox10 mutants unexpectedly showed more ltk-expressing cells than wild-type siblings. These cells remained in a premigratory position and expressed sox10 but not the earliest neural crest markers and may represent multipotent, but partially-restricted, progenitors. In summary, we have discovered a novel signalling pathway in NCC development and demonstrate fate specification of iridophores as the first identified role for Ltk.

MeSH Terms
Alleles Animals Apoptosis/genetics Carrier Proteins/genetics,metabolism Chromosome Mapping Embryonic Stem Cells/cytology,enzymology Gene Expression Regulation, Developmental High Mobility Group Proteins/genetics,metabolism Leukocytes/enzymology Melanocytes/cytology,enzymology Models, Biological Multipotent Stem Cells/cytology,enzymology Mutation Neural Crest/cytology,embryology,enzymology Phylogeny Protein-Tyrosine Kinases/genetics,metabolism SOXE Transcription Factors Zebrafish/embryology,genetics,metabolism Zebrafish Proteins/genetics,metabolism
Chemicals
Carrier Proteins High Mobility Group Proteins SOXE Transcription Factors Zebrafish Proteins sox10 protein, zebrafish Protein-Tyrosine Kinases
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Lopes Susana S
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
Yang Xueyan
Müller Jeanette
Carney Thomas J
McAdow Anthony R
Rauch Gerd-Jörg
Jacoby Arie S
Hurst Laurence D
Delfino-Machín Mariana
Haffter Pascal
Geisler Robert
Johnson Stephen L
Ward Andrew
Kelsh Robert N
Conflict of Interest

The authors have declared that no competing interests exist.

References (61)
61 references, click to expand
  1. Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila.
    Cell. 2007 Mar 9;128(5):961-75 PMID: 17350579
  2. Transcriptional regulation of mitfa accounts for the sox10 requirement in zebrafish melanophore development.
    Development. 2003 Jun;130(12):2809-18 PMID: 12736222
  3. Zebrafish YAC, BAC, and PAC genomic libraries.
    Methods Cell Biol. 1999;60:235-58 PMID: 9891341
  4. Sorting out Sox10 functions in neural crest development.
    Bioessays. 2006 Aug;28(8):788-98 PMID: 16927299
  5. An SCF-like ubiquitin ligase complex that controls presynaptic differentiation.
    Nature. 2004 Jul 15;430(6997):345-50 PMID: 15208641
  6. Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signaling.
    Development. 2001 Oct;128(20):3949-61 PMID: 11641219
  7. Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3.
    Hum Genet. 2000 Jul;107(1):1-6 PMID: 10982026
  8. An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio.
    Development. 2000 Jul;127(14):3031-44 PMID: 10862741
  9. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
    Nature. 2007 Aug 2;448(7153):561-6 PMID: 17625570
  10. Regulation of the microphthalmia-associated transcription factor gene by the Waardenburg syndrome type 4 gene, SOX10.
    J Biol Chem. 2000 Oct 6;275(40):30757-60 PMID: 10938265
  11. Sox10 haploinsufficiency affects maintenance of progenitor cells in a mouse model of Hirschsprung disease.
    Hum Mol Genet. 2002 Nov 15;11(24):3075-85 PMID: 12417529
  12. Common origin of pigment cells.
    Science. 1979 Feb 2;203(4379):410-5 PMID: 760198
  13. Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent.
    Mech Dev. 2005 May;122(5):659-69 PMID: 15817223
  14. Multipotentiality of the neural crest.
    Curr Opin Genet Dev. 2003 Oct;13(5):529-36 PMID: 14550420
  15. Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain.
    J Biol Chem. 1995 Jun 16;270(24):14247-50 PMID: 7782276
  16. Temperature-sensitive mutations that cause stage-specific defects in Zebrafish fin regeneration.
    Genetics. 1995 Dec;141(4):1583-95 PMID: 8601496
  17. Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates.
    Development. 2001 Nov;128(21):4113-25 PMID: 11684650
  18. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome.
    Hum Mol Genet. 2000 Aug 12;9(13):1907-17 PMID: 10942418
  19. Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2.
    J Biol Chem. 2000 Dec 1;275(48):37978-83 PMID: 10973953
  20. Genetic screen for mutations affecting development and function of the enteric nervous system.
    Dev Dyn. 2007 Jan;236(1):118-27 PMID: 17131406
  21. Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos.
    Development. 1993 Dec;119(4):1203-15 PMID: 8306883
  22. Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling.
    EMBO J. 2002 Jun 3;21(11):2703-14 PMID: 12032083
  23. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences.
    Nat Genet. 1994 Nov;8(3):256-63 PMID: 7874168
  24. Expression of snail2, a second member of the zebrafish snail family, in cephalic mesendoderm and presumptive neural crest of wild-type and spadetail mutant embryos.
    Dev Biol. 1995 Nov;172(1):86-99 PMID: 7589816
  25. TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics.
    BMC Evol Biol. 2004 Jun 28;4:18 PMID: 15222900
  26. A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms.
    Development. 1996 Dec;123:451-60 PMID: 9007262
  27. A crucial role for the Anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster.
    EMBO Rep. 2003 Aug;4(8):781-6 PMID: 12855999
  28. The zebrafish colourless gene regulates development of non-ectomesenchymal neural crest derivatives.
    Development. 2000 Feb;127(3):515-25 PMID: 10631172
  29. Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus.
    Hum Mol Genet. 2004 Jan 15;13(2):171-9 PMID: 14695357
  30. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)
    Oncogene. 1997 May 8;14(18):2175-88 PMID: 9174053
  31. MRBAYES: Bayesian inference of phylogenetic trees.
    Bioinformatics. 2001 Aug;17(8):754-5 PMID: 11524383
  32. Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor.
    Development. 1997 Jun;124(12):2377-86 PMID: 9199364
  33. Growth factors regulating neural crest cell fate decisions.
    Adv Exp Med Biol. 2006;589:197-205 PMID: 17076283
  34. An analysis of abdominal-B expression in the locust Schistocerca gregaria.
    Development. 1993 Jan;117(1):293-305 PMID: 7900987
  35. Genetic analysis of melanophore development in zebrafish embryos.
    Dev Biol. 2000 Sep 15;225(2):277-93 PMID: 10985850
  36. The transcription factor Sox10 is a key regulator of peripheral glial development.
    Genes Dev. 2001 Jan 1;15(1):66-78 PMID: 11156606
  37. Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development.
    Development. 1999 Aug;126(15):3425-36 PMID: 10393121
  38. Mutations at the W locus affect survival of neural crest-derived melanocytes in the mouse.
    Mech Dev. 1995 Apr;50(2-3):139-50 PMID: 7619726
  39. Specific pan-neural crest expression of zebrafish Crestin throughout embryonic development.
    Dev Dyn. 2001 Feb;220(2):169-74 PMID: 11169850
  40. Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio.
    Dev Biol. 2000 Nov 15;227(2):294-306 PMID: 11071756
  41. Activation of the receptor tyrosine kinase Kit is required for the proliferation of melanoblasts in the mouse embryo.
    Dev Biol. 1997 Dec 1;192(1):99-107 PMID: 9405100
  42. Human ltk: gene structure and preferential expression in human leukemic cells.
    Oncogene Res. 1990;5(3):199-204 PMID: 2320375
  43. The ltk receptor tyrosine kinase is expressed in pre-B lymphocytes and cerebral neurons and uses a non-AUG translational initiator.
    EMBO J. 1990 Jul;9(7):2279-87 PMID: 2357970
  44. Genetic control of adult pigment stripe development in zebrafish.
    Dev Biol. 1995 Jan;167(1):27-33 PMID: 7851648
  45. fork head domain genes in zebrafish.
    Dev Genes Evol. 1998 Jul;208(5):245-58 PMID: 9683740
  46. Genetics and evolution of pigment patterns in fish.
    Pigment Cell Res. 2004 Aug;17(4):326-36 PMID: 15250934
  47. Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway.
    Genes Dev. 2000 Jan 15;14(2):158-62 PMID: 10652270
  48. Receptor tyrosine kinase-dependent neural crest migration in response to differentially localized growth factors.
    Bioessays. 1997 Apr;19(4):337-45 PMID: 9136631
  49. Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion.
    Nature. 2003 Oct 2;425(6957):512-6 PMID: 14523447
  50. nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate.
    Development. 1999 Sep;126(17):3757-67 PMID: 10433906
  51. Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a.
    J Biol Chem. 2000 May 12;275(19):14013-6 PMID: 10747853
  52. SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells.
    Neuron. 2003 Apr 10;38(1):17-31 PMID: 12691661
  53. Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers.
    Nature. 2003 Oct 2;425(6957):507-12 PMID: 14523446
  54. Soluble and cell-bound forms of steel factor activity play distinct roles in melanocyte precursor dispersal and survival on the lateral neural crest migration pathway.
    Development. 1995 Mar;121(3):731-42 PMID: 7536655
  55. Sumoylation of the SOX10 transcription factor regulates its transcriptional activity.
    FEBS Lett. 2006 Mar 6;580(6):1635-41 PMID: 16494873
  56. Sequential segregation and fate of developmentally restricted intermediate cell populations in the neural crest lineage.
    Curr Top Dev Biol. 1991;25:133-53 PMID: 1660392
  57. Leukocytes express a novel gene encoding a putative transmembrane protein-kinase devoid of an extracellular domain.
    Nature. 1988 Jun 16;333(6174):672-6 PMID: 2836739
  58. A direct role for Sox10 in specification of neural crest-derived sensory neurons.
    Development. 2006 Dec;133(23):4619-30 PMID: 17065232
  59. Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration.
    Development. 2000 Sep;127(17):3715-24 PMID: 10934016
  60. Zebrafish pigmentation mutations and the processes of neural crest development.
    Development. 1996 Dec;123:369-89 PMID: 9007256
  61. Crystal structure of the tyrosine kinase domain of the human insulin receptor.
    Nature. 1994 Dec 22-29;372(6508):746-54 PMID: 7997262
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000026
Published
2008-03-07
Epub
2008-00-07
Pages
e1000026
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2265441
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056988 · United States
Wellcome Trust · United Kingdom
NIGMS NIH HHS · GM56988 · United States
NIGMS NIH HHS · R56 GM056988 · United States
Medical Research Council · G0300415 · United Kingdom
Medical Research Council · G0400806 · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.pgen.1000026 PMC Full Text View journal details
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