scholarly journals Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

2019 ◽  
Author(s):  
Lauren Saunders ◽  
Abhishek Mishra ◽  
Andrew J Aman ◽  
Victor Lewis ◽  
Matthew B Toomey ◽  
...  

Circulating endocrine factors are critical for orchestrating complex developmental processes during the generation of adult form. One such factor, thyroid hormone, regulates diverse cellular processes during post-embryonic development and can drive disparate morphological outcomes through mechanisms that remain essentially unknown. We sought to define how thyroid hormone elicits opposite responses in the abundance of two pigment cell classes during development of the zebrafish adult pigment pattern. By profiling individual transcriptomes from thousands of neural crest derived cells, including pigment cells, we reconstructed developmental trajectories and identified lineage-specific changes in response to thyroid hormone. Our findings show that thyroid hormone and its receptors regulate distinct events of cellular maturation across lineages, and illustrate how a single, global factor integrates seemingly divergent morphogenetic outcomes across developmental time.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Lauren M Saunders ◽  
Abhishek K Mishra ◽  
Andrew J Aman ◽  
Victor M Lewis ◽  
Matthew B Toomey ◽  
...  

Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form.


2021 ◽  
Author(s):  
Andrew J Aman ◽  
Lauren M Saunders ◽  
Sanjay R Srivatsan ◽  
Cole Trapnell ◽  
David M. Parichy

Regulation of neural crest derived pigment cells and dermal cells that form skin appendages is broadly similar across vertebrate taxa. In zebrafish, organized pigment stripes and an array of calcified scales form simultaneously in the skin during post-embryonic development. Understanding mechanisms that regulate stripe patterning and dermal morphogenesis may lead to discovery of fundamental mechanisms that govern development of animal form. To learn about cell types and potential signaling interactions that govern skin patterning and morphogenesis we generated and analyzed single cell transcriptomes of skin with genetic or induced defects in pigmentation and squamation. These data reveal a previously undescribed population of ameloblast-like epidermal cells, suggest hormonal control of epithelial-mesenchymal signaling, clarify the signaling network that governs scale papillae development, and identify the hypodermis as a crucial pigment cell support environment. These analyses provide new insights into the development of skin and pigmentation and highlight the utility of zebrafish for uncovering essential features of post-embryonic development in vertebrates.


2019 ◽  
Author(s):  
Lauren M Saunders ◽  
Abhishek K Mishra ◽  
Andrew J Aman ◽  
Victor M Lewis ◽  
Matthew B Toomey ◽  
...  

2020 ◽  
Vol 62 (1) ◽  
pp. 12-24
Author(s):  
Bibek Dutta ◽  
Taichi Asami ◽  
Tohru Imatomi ◽  
Kento Igarashi ◽  
Kento Nagata ◽  
...  

Abstract Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53+/−, p53−/−) and Hd-rR HNI hybrid (p53+/−) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53+/− fish than in p53−/− fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.


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):  
Alec K. Gramann ◽  
Arvind M. Venkatesan ◽  
Melissa Guerin ◽  
Craig J. Ceol

AbstractPreventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on mitfa, an ortholog of MITF, a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.


Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 1-21
Author(s):  
D. J. Pritchard ◽  
R. M. Clayton ◽  
D. I. De Pomerai

The in vitro transdifferentiation of chicken embryo neural retina into pigment epithelium and lens cells was investigated under a variety of experimental conditions. Our findings suggest that some aspects of the phenomena are a function of medium composition and volume, whereas others depend upon conditions which develop during culture growth. Before melanin is visible, potential pigment cells are recognized as foci within epithelialsheets which remain in contact with the dish. The final area occupied by colonies of potential pigment cells is directly proportional to bicarbonate concentration. Low total medium volume also favours formation of potential pigment cells. In contrast the extent of cells other than potential pigment cells is not related to bicarbonate and is favoured when the volume of medium is large. Accumulation of melanin within the potential pigment cell colonies is suppressed when cells are crowded together. Lentoid bodies are formed from cells which are distinct from potential pigment cells and arise in crowded situations, in association with multilayering. Another type of structure superficially resembling a lentoid is derived from cell aggregates formed during the initial establishment of cultures. The survival of these ‘aggregate bodies’ is inversely related to bicarbonate concentration. Crystallin content is unrelated to lentoid numbers. The results provide the basis for a new hypothesis concerning cytodifferentiation in this system.


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