On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish

Pigment cells in vertebrates are derived from the neural crest (NC), a pluripotent and migratory embryonic cell population. In fishes, larval melanophores develop during embryogenesis directly from NC cells migrating along dorsolateral and ventromedial paths. The embryonic origin of the melanophores that emerge during juvenile development in the skin to contribute to the striking colour patterns of adult fishes remains elusive. We have identified a small set of melanophore progenitor cells (MPs) in the zebrafish (Danio rerio, Cyprinidae) that is established within the first 2 days of embryonic development in close association with the segmentally reiterated dorsal root ganglia (DRGs). Lineage analysis and 4D in vivo imaging indicate that progeny of these embryonic MPs spread segmentally, giving rise to the melanophores that create the adult melanophore stripes. Upon depletion of larval melanophores by morpholino knockdown of Mitfa, the embryonic MPs are prematurely activated; their progeny migrate along the spinal nerves restoring the larval pattern and giving rise to postembryonic MPs associated with the spinal nerves. Mutational or chemical inhibition of ErbB receptors blocks all early NC migration along the ventromedial path, causing a loss of DRGs and embryonic MPs. We show that the sparse like (slk) mutant lacks larval and metamorphic melanophores and identify kit ligand a (kitlga) as the underlying gene. Our data suggest that kitlga is required for the establishment or survival of embryonic MPs. We propose a model in which DRGs provide a niche for the stem cells of adult melanophores.

[1]  M. Surani,et al.  Membrane-Bound Steel Factor Maintains a High Local Concentration for Mouse Primordial Germ Cell Motility, and Defines the Region of Their Migration , 2011, PloS one.

[2]  C. Moens,et al.  A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration , 2011, Development.

[3]  Stephen L. Johnson,et al.  Lineage Relationship of Direct-Developing Melanocytes and Melanocyte Stem Cells in the Zebrafish , 2011, PloS one.

[4]  D. Parichy,et al.  Post-Embryonic Nerve-Associated Precursors to Adult Pigment Cells: Genetic Requirements and Dynamics of Morphogenesis and Differentiation , 2011, PLoS genetics.

[5]  Stephen L. Johnson,et al.  mitfa is required at multiple stages of melanocyte differentiation but not to establish the melanocyte stem cell. , 2011, Developmental biology.

[6]  Stephen L. Johnson,et al.  Differential contribution of direct-developing and stem cell-derived melanocytes to the zebrafish larval pigment pattern. , 2010, Developmental biology.

[7]  U. Suter,et al.  Schwann Cell Precursors from Nerve Innervation Are a Cellular Origin of Melanocytes in Skin , 2009, Cell.

[8]  J. Lister,et al.  Foxd3 controls melanophore specification in the zebrafish neural crest by regulation of Mitf. , 2009, Developmental biology.

[9]  Stephen L. Johnson,et al.  Defects in ErbB-Dependent Establishment of Adult Melanocyte Stem Cells Reveal Independent Origins for Embryonic and Regeneration Melanocytes , 2009, PLoS genetics.

[10]  Ying Gu,et al.  Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration , 2009, Development.

[11]  C. Nüsslein-Volhard,et al.  ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration. , 2009, Developmental biology.

[12]  Meredith E. Protas,et al.  Evolution of coloration patterns. , 2008, Annual review of cell and developmental biology.

[13]  D. Parichy,et al.  Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation , 2008, Development.

[14]  J. Eisen,et al.  Neuregulin-mediated ErbB3 signaling is required for formation of zebrafish dorsal root ganglion neurons , 2008, Development.

[15]  Robert Geisler,et al.  Large-scale mapping of mutations affecting zebrafish development , 2007, BMC Genomics.

[16]  Stephen L. Johnson,et al.  Gene Duplication of the Zebrafish kit ligand and Partitioning of Melanocyte Development Functions to kit ligand a , 2007, PLoS genetics.

[17]  R. Kelsh,et al.  A direct role for Sox10 in specification of neural crest-derived sensory neurons , 2006, Development.

[18]  Stephen L. Johnson,et al.  Small molecule-induced ablation and subsequent regeneration of larval zebrafish melanocytes , 2006, Development.

[19]  P. Insel,et al.  A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern , 2006, Science.

[20]  W. Talbot,et al.  erbb3 and erbb2 Are Essential for Schwann Cell Migration and Myelination in Zebrafish , 2005, Current Biology.

[21]  J. M. Turner,et al.  Pigment pattern evolution by differential deployment of neural crest and post-embryonic melanophore lineages in Danio fishes , 2004, Development.

[22]  Alexandra Roulin.  The evolution, maintenance and adaptive function of genetic colour polymorphism in birds , 2004, Biological reviews of the Cambridge Philosophical Society.

[23]  Stephen L. Johnson,et al.  A requirement for kit in embryonic zebrafish melanocyte differentiation is revealed by melanoblast delay , 2004, Development Genes and Evolution.

[24]  Stephen L. Johnson,et al.  Temporal and molecular separation of the kit receptor tyrosine kinase's roles in zebrafish melanocyte migration and survival. , 2003, Developmental biology.

[25]  R. Kelsh,et al.  Transcriptional regulation of mitfa accounts for the sox10 requirement in zebrafish melanophore development , 2003, Development.

[26]  J. M. Turner,et al.  Essential role for puma in development of postembryonic neural crest-derived cell lineages in zebrafish. , 2003, Developmental biology.

[27]  J. Lister,et al.  Development of pigment cells in the zebrafish embryo , 2002, Microscopy research and technique.

[28]  Stephen L. Johnson,et al.  How the zebrafish gets its stripes. , 2001, Developmental biology.

[29]  R. Kelsh,et al.  Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates. , 2001, Development.

[30]  B. Wehrle-Haller,et al.  Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival. , 2001, Developmental biology.

[31]  S. Ekker,et al.  Effective targeted gene ‘knockdown’ in zebrafish , 2000, Nature Genetics.

[32]  Stephen L. Johnson,et al.  nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. , 1999, Development.

[33]  Stephen L. Johnson,et al.  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. , 1999, Development.

[34]  C. Nüsslein-Volhard,et al.  Zebrafish pigmentation mutations and the processes of neural crest development. , 1996, Development.

[35]  C. Nüsslein-Volhard,et al.  Mutations affecting development of the zebrafish inner ear and lateral line. , 1996, Development.

[36]  C. Nüsslein-Volhard,et al.  Mutations affecting pigmentation and shape of the adult zebrafish , 1996, Development Genes and Evolution.

[37]  E. Huang,et al.  Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. , 1992, Molecular biology of the cell.

[38]  D. Housman,et al.  The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene , 1988, Cell.

[39]  G. Streisinger,et al.  Segregation analyses and gene-centromere distances in zebrafish. , 1986, Genetics.

[40]  C. Gans,et al.  Neural Crest and the Origin of Vertebrates: A New Head , 1983, Science.

[41]  P. Pye-Smith.  The Descent of Man, and Selection in Relation to Sex , 1871, Nature.

[42]  J. Eisen,et al.  Neuregulin-mediated ErbB 3 signaling is required for formation of zebrafish dorsal root ganglion neurons , 2008 .

[43]  B. Thisse,et al.  High-resolution in situ hybridization to whole-mount zebrafish embryos , 2007, Nature Protocols.

[44]  Stephen L. Johnson,et al.  Genetic control of adult pigment stripe development in zebrafish. , 1995, Developmental biology.