scholarly journals Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyo Sik Jang ◽  
Yujie Chen ◽  
Jiaxin Ge ◽  
Alicia N. Wilkening ◽  
Yiran Hou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Neural Crest ◽  
Cell Fate ◽  
Pigment Cell ◽  
Chromatin Accessibility ◽  
Pigment Cells ◽  
Epigenetic Landscape ◽  
Cell Fate Decisions ◽  
Neural Crest Differentiation

Abstract Background Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood. Results We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a’s potential regulatory role in guanine synthesis pathway. Conclusions Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor.

nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3757-3767 ◽  
Author(s):  
J.A. Lister ◽  
C.P. Robertson ◽  
T. Lepage ◽  
S.L. Johnson ◽  
D.W. Raible
Keyword(s):  
Transcription Factor ◽  
Retinal Pigment Epithelium ◽  
Neural Crest ◽  
Cell Fate ◽  
Pigment Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Pigment Cells ◽  
Evolutionary Divergence ◽  
Wild Type

We report the isolation and identification of a new mutation affecting pigment cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mutants lack melanophores throughout development but have increased numbers of iridophores. The non-crest-derived retinal pigment epithelium is normal, suggesting that the mutation does not affect pigment synthesis per se. Expression of early melanoblast markers is absent in nacre mutants and transplant experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop-helix/leucine zipper transcription factor related to microphthalmia (Mitf), a gene known to be required for development of eye and crest pigment cells in the mouse. Transient expression of the wild-type nacre gene restored melanophore development in nacre(−/−) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstrate that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the retinal pigment epithelium in the fish is not nacre-dependent, suggesting an evolutionary divergence in the function of this gene.

scholarly journals Cell Fate Decisions in the Neural Crest, from Pigment Cell to Neural Development

2021 ◽  
Vol 22 (24) ◽  
pp. 13531
Author(s):  
Jonathan H. P. Dawes ◽  
Robert N. Kelsh
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Development ◽  
Pigment Cell ◽  
Dynamic Modelling ◽  
Cell Types ◽  
Pigment Cells ◽  
Cell Fate Decisions ◽  
Modelling Studies ◽  
Novel Model

The neural crest shows an astonishing multipotency, generating multiple neural derivatives, but also pigment cells, skeletogenic and other cell types. The question of how this process is controlled has been the subject of an ongoing debate for more than 35 years. Based upon new observations of zebrafish pigment cell development, we have recently proposed a novel, dynamic model that we believe goes some way to resolving the controversy. Here, we will firstly summarize the traditional models and the conflicts between them, before outlining our novel model. We will also examine our recent dynamic modelling studies, looking at how these reveal behaviors compatible with the biology proposed. We will then outline some of the implications of our model, looking at how it might modify our views of the processes of fate specification, differentiation, and commitment.

scholarly journals Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification

2019 ◽  
Author(s):  
Ricard Argelaguet ◽  
Hisham Mohammed ◽  
Stephen J Clark ◽  
L Carine Stapel ◽  
Christel Krueger ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Cell Fate ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
List Type ◽  
Germ Layer ◽  
Epigenetic Landscape ◽  
Germ Layers ◽  
Cell Fate Decisions

AbstractFormation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan. Recent studies employing single cell RNA-sequencing have identified major transcriptional changes associated with germ layer specification. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell fate choice remains unresolved, and the coordination between different epigenetic layers is unclear. Here we describe the first single cell triple-omics map of chromatin accessibility, DNA methylation and RNA expression during the exit from pluripotency and the onset of gastrulation in mouse embryos. We find dynamic dependencies between the different molecular layers, with evidence for distinct modes of epigenetic regulation. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of local lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements, driven by loss of methylation in enhancer marks and a concomitant increase of chromatin accessibility. In striking contrast, the epigenetic landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or epigenetically remodelled prior to overt cell fate decisions during gastrulation, providing the molecular logic for a hierarchical emergence of the primary germ layers.HighlightsFirst map of mouse gastrulation using comprehensive single cell triple-omic analysis.Exit from pluripotency is associated with a global repressive epigenetic landscape, driven by a sharp gain of DNA methylation and a gradual decrease of chromatin accessibility.DNA methylation and chromatin accessibility changes in enhancers, but not in promoters, are associated with germ layer formation.Mesoderm and endoderm enhancers become open and demethylated upon lineage commitment.Ectoderm enhancers are primed in the early epiblast and protected from the global repressive dynamics, supporting a default model of ectoderm commitment in vivo.

scholarly journals An analysis of pigment cell development in the periodic albino mutant of Xenopus

Development ◽  
1979 ◽  
Vol 52 (1) ◽  
pp. 165-170
Author(s):  
Gillian J. MacMillan
Keyword(s):  
Cell Differentiation ◽  
Neural Crest ◽  
Pigment Cell ◽  
Cell Development ◽  
Pigment Cells ◽  
Wild Type ◽  
Mutant Effect ◽  
Albino Mutant ◽  
Cells Cultured ◽  
Periodic Albino

The periodic albino mutant (apap) of Xenopus in which the development of melanophoresis impaired, is further reported here to possess an aberrant pattern of iridophore differentiation. The development of mutant and wild-type neural crest explants isolated in vesicles derived from tissues from identical and different genotypes was examined to determine if the mutant effect resides in the pigment cells or is mediated by the environmental tissues. Mutant melanophores and iridophores cultured in either mutant or wild-type tissues exhibited mutant patterns of differentiation. Wild-type pigment cells cultured in both wild-type and mutant tissues exhibited wild-type patterns of differentiation. Hence the mutation affects the capacities of melanoblasts and iridoblasts to differentiate but not the ability of the environmental tissues to support pigment cell differentiation.

scholarly journals Epigenetic Landscape Models: The Post-Genomic Era

2014 ◽  
Author(s):  
Jose Davila-Velderrain ◽  
Juan Carlos Martinez-Garcia ◽  
Elena R Alvarez-Buylla
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Computational Models ◽  
Theoretical Models ◽  
Cell Types ◽  
State Transitions ◽  
Epigenetic Landscape ◽  
Cell Fate Decisions ◽  
Landscape Models

Complex networks of regulatory interactions orchestrate developmental processes in multicellular organisms. Such a complex internal structure intrinsically constrains cellular behavior allowing only a reduced set of attainable and observable cellular states or cell types. Thus, a multicellular system undergoes cell fate decisions in a robust manner in the course of its normal development. The epigenetic landscape (EL) model originally proposed by C.H. Waddington was an early attempt to integrate these processes in a universal conceptual model of development. Since then, a wealth of experimental data has accumulated, the general mechanisms of gene regulation have been uncovered, and the placement of specific molecular components within modular gene regulatory networks (GRN) has become a common practice. This has motivated the development of mathematical and computational models inspired by the EL aiming to integrate molecular data and gain a better understanding of development, and hopefully predict cell differentiation and reprogramming events. Both deterministic and stochastic dynamical models have been used to described cell state transitions. In this review, we describe recent EL models, emphasising that the construction of an explicit landscape from a GRN is not the only way to implement theoretical models consistent with the conceptual basis of the EL. Moreover, models based on the EL have been shown to be useful in the study of morphogenic processes and not just cell differentiation. Here we describe the distinct approaches, comparing their strengths and weaknesses and the kind of biological questions that they have been able to address. We also point to challenges ahead.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

scholarly journals Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Gemma Sutton ◽  
Robert N. Kelsh ◽  
Steffen Scholpp
Keyword(s):  
Neural Crest ◽  
Pigment Cell ◽  
Model Organism ◽  
Neural Plate ◽  
The Body ◽  
Signalling Pathway ◽  
Border Region ◽  
Pigment Cells ◽  
Neural Plate Border

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.

scholarly journals Uncovering the mesendoderm gene regulatory network through multi-omic data integration

2020 ◽  
Author(s):  
Camden Jansen ◽  
Kitt D. Paraiso ◽  
Jeff J. Zhou ◽  
Ira L. Blitz ◽  
Margaret B. Fish ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Data Sets ◽  
List Type ◽  
Rna Seq ◽  
Data Types ◽  
Cell Fate Decisions ◽  
Gene Regulatory ◽  
Genome Scale ◽  
Omic Data

SummaryMesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low-throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data comprised of more than two data types is challenging. Here, we use linked self-organizing maps to combine ChIP-seq/ATAC-seq with temporal, spatial and perturbation RNA-seq data from Xenopus tropicalis mesendoderm development to build a high resolution genome scale mechanistic GRN. We recovered both known and previously unsuspected TF-DNA/TF-TF interactions and validated through reporter assays. Our analysis provides new insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly-dimensional multi-omic data sets.HighlightsBuilt a generally applicable pipeline to creating GRNs using highly-dimensional multi-omic data setsPredicted new TF-DNA/TF-TF interactions during mesendoderm developmentGenerate the first genome scale GRN for vertebrate mesendoderm and expanded the core mesendodermal developmental network with high fidelityDeveloped a resource to visualize hundreds of RNA-seq and ChIP-seq data using 2D SOM metaclusters.

scholarly journals Regulation of melanocyte development by ligand-dependent BMP signaling underlies oncogenic BMP signaling in melanoma

2019 ◽  
Author(s):  
Alec K. Gramann ◽  
Arvind M. Venkatesan ◽  
Melissa Guerin ◽  
Craig J. Ceol
Keyword(s):  
Neural Crest ◽  
Pigment Cell ◽  
Terminal Differentiation ◽  
Melanoma Cells ◽  
Cell Development ◽  
Bmp Signaling ◽  
Pigment Cells ◽  
Cell Type ◽  
Neural Crest Development ◽  
Direct Regulation

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.

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