PUBLICATION

Leukocyte tyrosine kinase functions in pigment cell development

Authors

Lopes, S.S., Yang, X., Müller, J., Carney, T.J., McAdow, A.R., Rauch, G.J., Jacoby, A.S., Hurst, L.D., Delfino-Machín, M., Haffter, P., Geisler, R., Johnson, S.L., Ward, A., and Kelsh, R.N.

ID

ZDB-PUB-080331-9

Date

2008

Source

PLoS Genetics 4(3): e1000026 (Journal)

Registered Authors

Carney, Tom, Geisler, Robert, Jacoby, Arie, Johnson, Stephen L., Kelsh, Robert, Lopes, Susana, McAdow, Ryan, Rauch, Gerd-Jörg, Yang, Xueyan

Keywords

Embryos, Zebrafish, Multiple alignment calculation, Phenotypes, Multipotency, Sequence alignment, Pigments, Neural crest

MeSH Terms

Alleles
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Animals
Mutation
Phylogeny
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism*
Melanocytes/cytology
Melanocytes/enzymology
Apoptosis/genetics
Models, Biological
Multipotent Stem Cells/cytology
Multipotent Stem Cells/enzymology
Leukocytes/enzymology
Neural Crest/cytology
Neural Crest/embryology
Neural Crest/enzymology
Protein-Tyrosine Kinases/genetics
Protein-Tyrosine Kinases/metabolism*
Gene Expression Regulation, Developmental
Embryonic Stem Cells/cytology
Embryonic Stem Cells/enzymology
Chromosome Mapping
High Mobility Group Proteins/genetics
High Mobility Group Proteins/metabolism
Carrier Proteins/genetics
Carrier Proteins/metabolism
SOXE Transcription Factors

(all 30)

PubMed

18369445 Full text @ PLoS Genet.

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 revene kinase (Ltk). Cell transplantation studies show that Ltk acts cell-autonomously within the iridophore lineage. Consistent with this, ltk is als 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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
ednrba	ltk^ty82/ty82	standard conditions	Protruding-mouth	Not Detected	iridophore	ISH	Fig. 3
ednrba	ltk^ty82/ty82	standard conditions	Long-pec	Not Detected	iridophore	ISH	Fig. 3
ednrba	WT	standard conditions	Long-pec		iridophore	ISH	Fig. 3
ednrba	WT	standard conditions	Protruding-mouth		iridophore	ISH	Fig. 3
EGFP	ba2Tg	standard conditions	Day 4		myelinating Schwann cell	IFL	Fig. S1
foxd3	sox10^t3/t3	standard conditions	Prim-5		neural crest	ISH	Fig. 6
foxd3	WT	standard conditions	Prim-5		neural crest	ISH	Fig. 6
ltk	ltk^ty82/ty82	standard conditions	Prim-5	Not Detected	immature eye	ISH	Fig. 3
ltk	ltk^ty82/ty82	standard conditions	Protruding-mouth	Not Detected	iridophore	ISH	Fig. 3
ltk	ltk^ty82/ty82	standard conditions	High-pec	Not Detected	iridophore	ISH	Fig. 3

1 - 10 of 40

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
ltk^j9e2/j9e2	standard conditions	Adult	eye iridophore decreased amount, abnormal	Fig. 1
ltk^j9e2/j9e2	standard conditions	Adult	iridophore decreased amount, abnormal	Fig. 1
ltk^j9s1/j9s1	standard conditions	Adult	eye iridophore decreased amount, abnormal	Fig. 1
ltk^j9s1/j9s1	standard conditions	Adult	iridophore decreased amount, abnormal	Fig. 1
ltk^j9s1/j9s1	standard conditions	Adult	melanocyte decreased amount, abnormal	Fig. 1
ltk^ty82/ty82	standard conditions	Protruding-mouth	eye iridophore decreased amount, abnormal	Fig. 1
ltk^ty82/ty82	standard conditions	Protruding-mouth	iridophore decreased amount, abnormal	Fig. 1
ltk^ty82/ty82	standard conditions	Day 5	cartilage element morphology, normal	Fig. S1
ltk^ty82/ty82	standard conditions	Day 5	melanocyte normal amount, normal	Fig. S1
ltk^ty82/ty82	standard conditions	Day 5	xanthophore normal amount, normal	Fig. S1

1 - 10 of 12

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ba2Tg	Tg(-4.9sox10:EGFP)	Transgenic Insertion
j9e1		Point Mutation	ltk
j9e2		Point Mutation	ltk
j9s1		Point Mutation	ltk
m618		Point Mutation	sox10
t3		Insertion	sox10
ty9		Unknown	ltk
ty70		Unknown	ltk
ty82		Point Mutation	ltk

1 - 9 of 9

Show

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
ba2Tg
ltk^j9e1/j9e1
ltk^j9e2/j9e2
ltk^j9s1/j9s1
ltk^ty9/ty9
ltk^ty70/ty70
ltk^ty82/ty82
sox10^m618/m618
sox10^t3/t3
WT

Antibodies

Orthology

Gene	Orthology
ltk

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Entity Type	Entity Symbol	Location
GENE	ltk	Chr: 17 Details
SSLP	z10985	Chr: 17 Details

Lopes et al., 2008 ZDB-PUB-080331-9 PMID:18369445

Leukocyte tyrosine kinase functions in pigment cell development

Lopes et al., 2008

ZDB-PUB-080331-9
PMID:18369445