Leukocyte tyrosine kinase functions in pigment cell development

Susana S. Lopes, Xueyan Y. Yang, Jeanette Muller, Thomas J. Carney, Anthony R. McAdow, Gerd-Jorg Rauch, Arie S. Jacoby, Laurence D. Hurst, Mariana Delfino-Machin, Pascal Haffter, Robert Geisler, Stephen L. Johnson, Andrew Ward, Robert N. Kelsh

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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.
Original languageEnglish
Article numbere1000026
Number of pages13
JournalPlos Genetics
Volume4
Issue number3
DOIs
Publication statusPublished - 7 Mar 2008

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Neural Crest
Protein-Tyrosine Kinases
neural crest
tyrosine
pigment
leukocytes
phosphotransferases (kinases)
Leukocytes
pigments
mutants
cells
Zebrafish
developmental biology
Danio rerio
transplantation
apoptosis
mutant
Developmental Biology
defect
Melanocytes

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Lopes, S. S., Yang, X. Y., Muller, J., Carney, T. J., McAdow, A. R., Rauch, G-J., ... Kelsh, R. N. (2008). Leukocyte tyrosine kinase functions in pigment cell development. Plos Genetics, 4(3), [e1000026]. https://doi.org/10.1371/journal.pgen.1000026

Leukocyte tyrosine kinase functions in pigment cell development. / Lopes, Susana S.; Yang, Xueyan Y.; Muller, Jeanette; Carney, Thomas J.; McAdow, Anthony R.; Rauch, Gerd-Jorg; Jacoby, Arie S.; Hurst, Laurence D.; Delfino-Machin, Mariana; Haffter, Pascal; Geisler, Robert; Johnson, Stephen L.; Ward, Andrew; Kelsh, Robert N.

In: Plos Genetics, Vol. 4, No. 3, e1000026, 07.03.2008.

Research output: Contribution to journalArticle

Lopes, SS, Yang, XY, Muller, J, Carney, TJ, McAdow, AR, Rauch, G-J, Jacoby, AS, Hurst, LD, Delfino-Machin, M, Haffter, P, Geisler, R, Johnson, SL, Ward, A & Kelsh, RN 2008, 'Leukocyte tyrosine kinase functions in pigment cell development', Plos Genetics, vol. 4, no. 3, e1000026. https://doi.org/10.1371/journal.pgen.1000026
Lopes SS, Yang XY, Muller J, Carney TJ, McAdow AR, Rauch G-J et al. Leukocyte tyrosine kinase functions in pigment cell development. Plos Genetics. 2008 Mar 7;4(3). e1000026. https://doi.org/10.1371/journal.pgen.1000026
Lopes, Susana S. ; Yang, Xueyan Y. ; Muller, Jeanette ; Carney, Thomas J. ; McAdow, Anthony R. ; Rauch, Gerd-Jorg ; Jacoby, Arie S. ; Hurst, Laurence D. ; Delfino-Machin, Mariana ; Haffter, Pascal ; Geisler, Robert ; Johnson, Stephen L. ; Ward, Andrew ; Kelsh, Robert N. / Leukocyte tyrosine kinase functions in pigment cell development. In: Plos Genetics. 2008 ; Vol. 4, No. 3.
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