Cyclical fate restriction: a new view of neural crest cell fate specification

Kelsh, Robert N.; Sosa, Karen Camargo; Farjami, Saeed; Makeev, Vsevolod J.; Dawes, Jonathan; Rocco, Andrea

doi:10.1242/dev.176057

Cited by 28 publications

(45 citation statements)

References 151 publications

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“…In contrast, upregulation of Frizzled and Mitfa, following exposure to Wnt/β-catenin ligands and downregulation of Ltk and Tfec (and others) would drive the cell towards a melanocyte fate (Kelsh et al, 2021). It is conceivable that Wnt signalling plays a key role in the entry and exit from the NC-HMP cycling progenitor state and may act alongside other signals to initiate entry into the cycling state and to allow differentiation of each derivative fate from the cells in the cycling state (Farjami et al, 2021). The CFR model shares similarities with the so-called "phase-stage model", which has been proposed for embryonic stem (ES) cell fate restrictions following the observation that an ES cell can occupy a state, known as the phase stage when it can "explore" several potential states (distinguished by oscillating levels of Nanog; Miyanari and Torres-Padilla, 2012) over time (Garcia-Ojalvo and Martinez Arias, 2012).…”

Section: Models Of Nc Specificationmentioning

confidence: 97%

“…It is proposed that the priming is reflected in fluctuating expression levels of fate-specification receptors and key fate-specific transcription factors such as Mitfa. The CFR hypothesis suggests that adopting a specific fate occurs when the primed sub-state is exposed to sufficient levels and duration of the fate-specification ligand, driving the differentiation of a specific fate (Kelsh et al, 2021). Although the CFR hypothesis is, at this point, somewhat speculative, it is supported by several observations and by theoretical modelling studies (Farjami et al, 2021).…”

Section: Models Of Nc Specificationmentioning

confidence: 99%

“…The CFR hypothesis suggests that adopting a specific fate occurs when the primed sub-state is exposed to sufficient levels and duration of the fate-specification ligand, driving the differentiation of a specific fate (Kelsh et al, 2021). Although the CFR hypothesis is, at this point, somewhat speculative, it is supported by several observations and by theoretical modelling studies (Farjami et al, 2021). For example, the ltk, encoding a receptor tyrosine kinase, is crucial for iridophore specification but shows heterogeneous expression in premigratory NCCs (Lopes et al, 2008).…”

Section: Models Of Nc Specificationmentioning

confidence: 99%

“…Thus, the upregulation of Ltk and Tfec, as well as downregulation of, for example, a Frizzled receptor and Mitfa, all in response to exposure to ALKALs (ligands of Ltk) would result in an iridophore fate. In contrast, upregulation of Frizzled and Mitfa, following exposure to Wnt/β-catenin ligands and downregulation of Ltk and Tfec (and others) would drive the cell towards a melanocyte fate ( Kelsh et al, 2021 ). It is conceivable that Wnt signalling plays a key role in the entry and exit from the NC-HMP cycling progenitor state and may act alongside other signals to initiate entry into the cycling state and to allow differentiation of each derivative fate from the cells in the cycling state (Farjami et al, 2021).…”

Section: Models Of Nc Specificationmentioning

confidence: 99%

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

Sutton

Kelsh

Scholpp

2021

Front. Cell Dev. Biol.

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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.

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Section: Models Of Nc Specificationmentioning

confidence: 97%

Section: Models Of Nc Specificationmentioning

confidence: 99%

Section: Models Of Nc Specificationmentioning

confidence: 99%

Section: Models Of Nc Specificationmentioning

confidence: 99%

See 2 more Smart Citations

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

Sutton

Kelsh

Scholpp

2021

Front. Cell Dev. Biol.

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“…In contrast, a recent preprint that directly assesses the PFR model for pigment cell development in zebrafish has rejected the PFR hypothesis [16]. This has led us to reassess the debate, and we have recently proposed a novel cyclical fate restriction (CFR) hypothesis (Figure 1c) that can reconcile the conflicting evidence underpinning each of the DFR and PFR models [17]. Here, we will summarize that evidence, and outline the PFR model as an explanation of peripheral neural development.…”

Section: Introductionmentioning

confidence: 98%

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

Dawes

Kelsh

2021

IJMS

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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.

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Neural Crest: Origin, Migration and Differentiation

Sutton¹,

Kelsh²

2022

Encyclopedia of Life Sciences

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The neural crest is a population of cells that emigrates from the dorsal neural tube during early embryogenesis and migrates extensively to give rise to a myriad of cell types. Patterns of migration are controlled largely by extracellular cues in the environment. Neural crest cells are initially multipotent, but the mechanism whereby cells choose and become committed to individual fates remains a longstanding source of contention. Cell fate specification – the selection of an individual cell fate from all the possibilities available to a multipotent progenitor – is generally considered to be a progressive process. However, a recent flurry of single‐cell transcriptional profiling studies indicates a more dynamic process in which cells with retained multipotency display expression of competing genetic modules specifying different fates. Extracellular cues in the migratory and postmigratory environment act together with intrinsic transcription factors to ensure that specific fates are chosen. Key Concepts The neural crest is an important tissue, as reflected in its nickname, ‘the fourth germ layer’. Neural crest cells give rise to many different cell types. Neural crest cells are induced at the boundary of the developing neural plate and prospective epidermis. Neural crest induction depends on BMP signalling in the prospective epidermis and Wnt signalling from the underlying mesoderm. These signals induce neural crest in two phases, specification of the neural plate border, and specification/maintenance of definitive neural crest. Neural crest migration patterns are complex, and usually specific to the derivative fate adopted. Neural crest migration is controlled by the environmental distribution of repellent and attractive/permissive signals, with specific receptor expression in the neural crest cells determining their response. All neural crest cells are initially multipotent, with specification of individual derivative fates resulting from competition between genetic modules controlling pairs of fates. Nevertheless, it is proposed that these specified cells retain a cryptic full multipotency, most visible in adult neural crest‐derived stem cells. Neural crest fate specification is then a dynamic process in which extracellular factors influence the transcriptional state of the cell, eventually driving it towards a specific fate choice. Fate specification results from transcriptional activation of key genes encoding (a combination of) specific transcription factors. These transcription factors, together with ongoing extracellular signals, activate and maintain the fate‐specific gene regulatory networks that characterise each cell type.

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Cyclical fate restriction: a new view of neural crest cell fate specification

Cited by 28 publications

References 151 publications

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

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

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

Neural Crest: Origin, Migration and Differentiation

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