Leukocyte Tyrosine Kinase Functions in Pigment Cell Development
| Autor: | Mariana Delfino-Machin, Arie S. Jacoby, Xueyan Y. Yang, Laurence D. Hurst, Gerd-Jörg Rauch, Andrew Ward, Robert N. Kelsh, Susana S. Lopes, Stephen L. Johnson, Pascal Haffter, Robert Geisler, Anthony R. McAdow, Thomas J. Carney, Jeanette Muller |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
lcsh:QH426-470 SOX10 Apoptosis Models Biological 03 medical and health sciences 0302 clinical medicine Genetics Developmental Biology/Developmental Molecular Mechanisms Leukocytes Animals Progenitor cell Molecular Biology Zebrafish Genetics (clinical) Ecology Evolution Behavior and Systematics Alleles Embryonic Stem Cells Phylogeny 030304 developmental biology 0303 health sciences biology SOXE Transcription Factors Multipotent Stem Cells High Mobility Group Proteins Neural crest Chromosome Mapping Gene Expression Regulation Developmental Protein-Tyrosine Kinases Zebrafish Proteins Xanthophore biology.organism_classification Embryonic stem cell Developmental Biology/Stem Cells lcsh:Genetics Multipotent Stem Cell Neural Crest embryonic structures Mutation Developmental Biology/Cell Differentiation Melanocytes Carrier Proteins Developmental biology 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS Genetics Lopes, S S, Yang, X Y, Muller, J, Carney, T J, McAdow, A R, Rauch, G-J, Jacoby, A S, Hurst, L D, Delfino-Machin, M, Haffter, P, Geisler, R, Johnson, S L, Ward, A & Kelsh, R N 2008, ' Leukocyte tyrosine kinase functions in pigment cell development ', Plos Genetics, vol. 4, no. 3, e1000026 . https://doi.org/10.1371/journal.pgen.1000026 PLoS Genetics, Vol 4, Iss 3, p e1000026 (2008) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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. Author Summary Stem and other multipotent cells generate diverse cell-types, but our understanding of how they make these decisions, which is important for their therapeutic use, is incomplete. Neural crest cells are an important class of multipotent cells and generate multiple stem cell types. We have looked at how pigment cells are made from the neural crest in the zebrafish. The silver shine familiar in so many fish is due to specialised mirror-like pigment cells, called iridophores. We show that these cells are missing in zebrafish shady mutants. We identify the shady gene as encoding a cell signalling receptor, leukocyte tyrosine kinase (Ltk), that has recently been associated with human auto-immune disease. We show that in zebrafish this gene is most likely required to make iridophores from neural crest cells. Thus, we identify a novel pathway required for diversification of these multipotent cells. Our work defines the first role for Ltk in a vertebrate. It provides a mutant resource that will allow us to discover the full breadth of roles for this important gene. Furthermore, the loss of iridophores forms a simple visual screen for inhibition of LTK function and might well have implications in drug discovery. |
| Databáze: | OpenAIRE |
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