scholarly journals Identification ofkit-ligand aas the Gene Responsible for the Medaka Pigment Cell Mutantfew melanophore

2019 ◽  
Author(s):  
Yuji Otsuki ◽  
Yuki Okuda ◽  
Kiyoshi Naruse ◽  
Hideyuki Saya

ABSTRACTThe body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. Thefew melanophore(fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identifykit-ligand a(kitlga) as the gene whose mutation gives rise to thefmphenotype. This identification was confirmed by generation ofkitlgaknockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue thefmmutant phenotype. We also found that expression ofsox5,pax7a,pax3a, andmitfagenes is down-regulated in bothfmandkitlgaknockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit–related pigmentation disorders such as piebaldism in humans, and ourkitlgaknockout medaka may prove useful as a tool for drug screening.

2019 ◽  
Vol 10 (1) ◽  
pp. 311-319 ◽  
Author(s):  
Yuji Otsuki ◽  
Yuki Okuda ◽  
Kiyoshi Naruse ◽  
Hideyuki Saya

The body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. The few melanophore (fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identify kit-ligand a (kitlga) as the gene whose mutation gives rise to the fm phenotype. This identification was confirmed by generation of kitlga knockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue the fm mutant phenotype. We also found that expression of sox5, pax7a, pax3a, and mitfa genes is down-regulated in both fm and kitlga knockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit–related pigmentation disorders such as piebaldism in humans, and our kitlga knockout medaka may prove useful as a tool for drug screening.


Author(s):  
Gemma Sutton ◽  
Robert N. Kelsh ◽  
Steffen Scholpp

The neural crest (NC) is a multipotent cell population in vertebrate embryos with extraordinary migratory capacity. The NC is crucial for vertebrate development and forms a myriad of cell derivatives throughout the body, including pigment cells, neuronal cells of the peripheral nervous system, cardiomyocytes and skeletogenic cells in craniofacial tissue. NC induction occurs at the end of gastrulation when the multipotent population of NC progenitors emerges in the ectodermal germ layer in the neural plate border region. In the process of NC fate specification, fate-specific markers are expressed in multipotent progenitors, which subsequently adopt a specific fate. Thus, NC cells delaminate from the neural plate border and migrate extensively throughout the embryo until they differentiate into various cell derivatives. Multiple signalling pathways regulate the processes of NC induction and specification. This review explores the ongoing role of the Wnt/β-catenin signalling pathway during NC development, focusing on research undertaken in the Teleost model organism, zebrafish (Danio rerio). We discuss the function of the Wnt/β-catenin signalling pathway in inducing the NC within the neural plate border and the specification of melanocytes from the NC. The current understanding of NC development suggests a continual role of Wnt/β-catenin signalling in activating and maintaining the gene regulatory network during NC induction and pigment cell specification. We relate this to emerging models and hypotheses on NC fate restriction. Finally, we highlight the ongoing challenges facing NC research, current gaps in knowledge, and this field’s potential future directions.


2019 ◽  
Author(s):  
Jonathan E. Valencia ◽  
Roberto Feuda ◽  
Dan O. Mellott ◽  
Robert D. Burke ◽  
Isabelle S. Peter

ABSTRACTOne of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, including pax6, six1/2, eya, and dac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.


2020 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Meagan Kurland ◽  
Bryn O’Meara ◽  
Dana K. Tucker ◽  
Brian D. Ackley

Nervous systems are comprised of diverse cell types that differ functionally and morphologically. During development, extrinsic signals, e.g., growth factors, can activate intrinsic programs, usually orchestrated by networks of transcription factors. Within that network, transcription factors that drive the specification of features specific to a limited number of cells are often referred to as terminal selectors. While we still have an incomplete view of how individual neurons within organisms become specified, reporters limited to a subset of neurons in a nervous system can facilitate the discovery of cell specification programs. We have identified a fluorescent reporter that labels VD13, the most posterior of the 19 inhibitory GABA (γ-amino butyric acid)-ergic motorneurons, and two additional neurons, LUAL and LUAR. Loss of function in multiple Wnt signaling genes resulted in an incompletely penetrant loss of the marker, selectively in VD13, but not the LUAs, even though other aspects of GABAergic specification in VD13 were normal. The posterior Hox gene, egl-5, was necessary for expression of our marker in VD13, and ectopic expression of egl-5 in more anterior GABAergic neurons induced expression of the marker. These results suggest egl-5 is a terminal selector of VD13, subsequent to GABAergic specification.


2020 ◽  
Author(s):  
Csaba Verasztó ◽  
Sanja Jasek ◽  
Martin Gühmann ◽  
Réza Shahidi ◽  
Nobuo Ueda ◽  
...  

AbstractNervous systems coordinate effectors across the body during movements. We know little about the cellular-level structure of synaptic circuits for such body-wide control. Here we describe the whole-body synaptic connectome and cell-type complement of a three-segmented larva of the marine annelid Platynereis dumerilii. We reconstructed and annotated over 1,500 neurons and 6,500 non-neuronal cells in a whole-body serial electron microscopy dataset. The differentiated cells fall into 180 neuronal and 90 non-neuronal cell types. We analyse the modular network architecture of the entire nervous system and describe polysynaptic pathways from 428 sensory neurons to four effector systems – ciliated cells, glands, pigment cells and muscles. The complete somatic musculature and its innervation will be described in a companion paper. We also investigated intersegmental differences in cell-type complement, descending and ascending pathways, and mechanosensory and peptidergic circuits. Our work provides the basis for understanding whole-body coordination in annelids.


Development ◽  
1991 ◽  
Vol 113 (4) ◽  
pp. 1085-1091 ◽  
Author(s):  
R.A. Cameron ◽  
S.E. Fraser ◽  
R.J. Britten ◽  
E.H. Davidson

This paper examines the cell lineage relationships and cell fates in embryos of the sea urchin Strongylocentrotus purpuratus leading to the various cell types derived from the definitive vegetal plate territory or the veg2 tier of cells. These cell types are gut, pigment cells, basal cells and coelomic pouches. They are cell types that constitute embryonic structures through cellular migration or rearrangement unlike the relatively non-motile ectoderm cell types. For this analysis, we use previous knowledge of lineage to assign macromeres to one of four types: VOM, the oral macromere; VAM, the aboral macromere, right and left VLM, the lateral macromeres. Each of the four macromeres contributes progeny to all of the cell types that descend from the definitive vegetal plate. Thus in the gut each macromere contributes to the esophagus, stomach and intestine, and the stripe of labeled cells descendant from a macromere reflects the re-arrangement of cells that occurs during archenteron elongation. Pigment cell contributions exhibit no consistent pattern among the four macromeres, and are haphazardly distributed throughout the ectoderm. Gut and pigment cell contributions are thus radially symmetrical. In contrast, the VOM blastomere contributes to both of the coelomic pouches while the other three macromeres contribute to only one or the other pouch. The total of the macromere contribution amounts to 60% of the cells constituting the coelomic pouches.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Margherita Perillo ◽  
Nathalie Oulhen ◽  
Stephany Foster ◽  
Maxwell Spurrell ◽  
Cristina Calestani ◽  
...  

Cells bearing pigment have diverse roles and are often under strict evolutionary selection. Here, we explore the regulation of pigmented cells in the purple sea urchin Strongylocentrotus purpuratus, an emerging model for diverse pigment function. We took advantage of single cell RNA-seq (scRNAseq) technology and discovered that pigment cells in the embryo segregated into two distinct populations, a mitotic cluster and a post-mitotic cluster. Gcm is essential for expression of several genes important for pigment function, but is only transiently expressed in these cells. We discovered unique genes expressed by pigment cells and test their expression with double fluorescence in situ hybridization. These genes include new members of the fmo family that are expressed selectively in pigment cells of the embryonic and in the coelomic cells of the adult - both cell-types having immune functions. Overall, this study identifies nodes of molecular intersection ripe for change by selective evolutionary pressures.


Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 47-62
Author(s):  
D. J. Pritchard

Neural retina from 8- to 9-day embryo chickens was grown in long-term cell culture in an experiment to test the hpothesis that one step during the in vitro transdifferentiation of neural retina into pigment cells occurs in response to stimulation of tricarboxylic acid (TCA) cycle activity. Time-lapse photography showed that pigment-cell formation occurs through the intermediate stages of ‘undistinguished cells’, ‘pavement epithelium’ and ‘potential pigment cells’. Mitosis of undistinguished cells to pavement epithelium was proportional to malonate over most of the tested range of concentrations and was inhibited by succinate, which respectively depress and stimulate the TCA cycle. Conversely mitosis of pavement epithelium to potential pigment cells occurred in proportion to succinate concentration over most of the tested range and was inhibited by malonate, in support of the hypothesis under test. Melanin synthesis begins in a minority of ‘pigment leader cells’ uniquely stimulated by the lowest concentration of malonate, although higher concentrations blocked pigment synthesis in all cell types. The pigment leader cells appear to act as centres of influence upon neighbouring potential pigment cells, which subsequently also beome pigmented. Lactate inhibited most or all of the steps in formation of pigment epithelium. Between three and five mitoses occur in the production of pigment cells, whereas multilayers and lentoid bodies seem to be formed by expansion of undistinguished cells, probably without mitosis. The observations lead to a general theory that metaplastic conversion between cell types in eye tissues may require the physical isolation of overtly differentiated, multipotent cells from ‘leader’ cells which normally hold them in physiological subjugation.


Author(s):  
Victor M. Lewis ◽  
Lauren M. Saunders ◽  
Tracy A. Larson ◽  
Emily J. Bain ◽  
Samantha L. Sturiale ◽  
...  

Understanding genetic and cellular bases of adult form remains a fundamental goal at the intersection of developmental and evolutionary biology. The skin pigment cells of vertebrates, derived from embryonic neural crest, are a useful system for elucidating mechanisms of fate specification, pattern formation, and how particular phenotypes impact organismal behavior and ecology. In a survey of Danio fishes, including the zebrafish Danio rerio, we identified two populations of white pigment cells—leucophores—one of which arises by transdifferentiation of adult melanophores and another of which develops from a yellow–orange xanthophore or xanthophore-like progenitor. Single-cell transcriptomic, mutational, chemical, and ultrastructural analyses of zebrafish leucophores revealed cell-type–specific chemical compositions, organelle configurations, and genetic requirements. At the organismal level, we identified distinct physiological responses of leucophores during environmental background matching, and we showed that leucophore complement influences behavior. Together, our studies reveal independently arisen pigment cell types and mechanisms of fate acquisition in zebrafish and illustrate how concerted analyses across hierarchical levels can provide insights into phenotypes and their evolution.


2021 ◽  
Author(s):  
Masataka Nikaido ◽  
Tatiana Subkhankulova ◽  
Leonid A. Uroshlev ◽  
Artem J. Kasianov ◽  
Karen Camargo Sosa ◽  
...  

Neural crest cells (NCCs) are highly multipotent stem cells. A long-standing controversy exists over the mechanism of NCC fate specification, specifically regarding the presence and potency of intermediate progenitors. The direct fate restriction (DFR) model, based on early in vivo clonal studies, hypothesised that intermediates are absent and that migrating cells maintain full multipotency. However, most authors favour progressive fate restriction (PFR) models, with fully multipotent early NCCs (ENCCs) transitioning to partially-restricted intermediates before committing to individual fates. Here, single cell transcriptional profiling of zebrafish pigment cell development leads to us proposing a Cyclical Fate Restriction mechanism of NCC development that reconciles the DFR and PFR models. Our clustering of single NCC Nanostring transcriptional profiles identifies only broadly multipotent intermediate states between ENCCs and differentiated melanocytes and iridophores. Leukocyte tyrosine kinase (Ltk) marks the multipotent progenitor and iridophores, consistent with biphasic ltk expression. Ltk inhibitor and constitutive activation studies support expression at an early multipotent stage, whilst lineage-tracing of ltk-expressing cells reveals their multipotency extends beyond pigment cell-types to neural fates. We conclude that pigment cell development does not involve a conventional PFR mechanism, but instead occurs directly and more dynamically from a broadly multipotent intermediate state.


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