Nodal signalling in embryogenesis and tumourigenesis

Quail, Daniela F.; Siegers, Gabrielle M.; Jewer, Michael; Postovit, Lynne-Marie

doi:10.1016/j.biocel.2012.12.021

Cited by 79 publications

(93 citation statements)

References 117 publications

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“…One possible reason for such complexity resides in the recognized contextdependency of Nodal function (reviewed in [1,3]). It is known, for example, that Nodal signalling can maintain pluripotency and prevent differentiation to neuroectoderm in human embryonic stem cells (hESC) and mouse epiblastderived stems cells (mEpiSC) [32] while it is necessary for endoderm differentiation in pluripotent cells and the mouse gastrula embryo [3,33].…”

Section: Context-dependency Of Nodal Functions In Nervous System Asymmentioning

confidence: 99%

Nodal signalling and asymmetry of the nervous system

Signore

Palma

Concha

2016

Phil. Trans. R. Soc. B

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One contribution of 17 to a theme issue 'Provocative questions in left -right asymmetry'. The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left-right asymmetry of the nervous system. This article is part of the themed issue 'Provocative questions in leftright asymmetry'.

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Section: Context-dependency Of Nodal Functions In Nervous System Asymmentioning

confidence: 99%

Nodal signalling and asymmetry of the nervous system

Signore

Palma

Concha

2016

Phil. Trans. R. Soc. B

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“…Nodal signals can act as morphogens and are essential at key moments and distinct tissues throughout development to determine primary body axes, ensure proper gastrulation and neural patterning, cardiogenesis, and the maintenance of embryonic stem cell pluripotency (reviewed in Shen 2007;Schier 2009;Quail et al, 2013). The regulation of the Nodal pathway involves a complex network of receptors, coreceptors, antagonists and intracellular proteins, as well as positive and negative feedback loops that together define cell proliferation, differentiation, and tissue morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

Evolution, divergence and loss of the Nodal signalling pathway: new data and a synthesis across the Bilateria

Grande¹,

Martín-Durán²,

Kenny³

et al. 2014

Int. J. Dev. Biol.

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Since the discovery that the TGF-b signalling molecule Nodal and its downstream effector Pitx have a parallel role in establishing asymmetry between molluscs and deuterostomes the debate over the degree to which this signalling pathway is conserved across the Bilateria as a whole has been ongoing. Further taxon sampling is critical to understand the evolution and divergence of this signalling pathway in animals. Using genome and transcriptome mining we confirmed the presence of nodal and Pitx in a range of additional animal taxa for which their presence has not yet been described. In situ hybridization was used to show the embryonic expression of these genes in brachiopods and planarians. We show that both nodal and Pitx genes are broadly conserved across the Spiralia, and nodal likely appeared in the Bilaterian stem lineage after the divergence of the Acoelomorpha. Furthermore, both nodal and Pitx mRNA appears to be expressed in an asymmetric fashion in the brachiopod Terebratalia transversa. No evidence for the presence of a Lefty ortholog could be found in the non-deuterostome genomic resources examined. Nodal expression is asymmetric in a number of spiralian lineages, indicating a possible ancestral role of the Nodal/ Pitx cascade in the establishment of asymmetries across the Bilateria.

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“…A similar vascularisation-promoting effect has been noted for breast cancers: Nodal signalling leads to the upregulation of pro-angiogenic factors in the tissue surrounding the tumour cells (Quail et al, 2013). Based on these observations, it is tempting to hypothesise that abnormally high activation of Nodal signalling in adult stem cells, combined with genetic mutations, could result in increased proliferation but also resistance to differentiation, thereby mimicking the mechanisms maintaining pluripotency of hPSCs.…”

Section: Activin/nodal Signalling In Cancer and Metastasismentioning

confidence: 68%

“…However, the function of Activin/Nodal signalling in the self-renewal or differentiation of adult stem cells is less clear, despite several recent reports suggesting a key role (Cambray et al, 2012;Dunphy et al, 2011;Kadaja et al, 2014). Indeed, the expression of Nodal seems to be limited to certain tissues which undergo considerable remodelling, such as the endometrium, placenta and lactating mammary gland (Quail et al, 2013;Strizzi et al, 2012). This suggests that Nodal might not be involved in the maintenance and specification of many adult stem cells, in contrast to TGFβ, which is more widely expressed.…”

Section: Activin/nodal Signalling In Adult Tissue Stem Cellsmentioning

confidence: 99%

Activin/Nodal signalling in stem cells

2015

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Activin/Nodal growth factors control a broad range of biological processes, including early cell fate decisions, organogenesis and adult tissue homeostasis. Here, we provide an overview of the mechanisms by which the Activin/Nodal signalling pathway governs stem cell function in these different stages of development. We describe recent findings that associate Activin/Nodal signalling to pathological conditions, focusing on cancer stem cells in tumorigenesis and its potential as a target for therapies. Moreover, we will discuss future directions and questions that currently remain unanswered on the role of Activin/Nodal signalling in stem cell selfrenewal, differentiation and proliferation.

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Nodal signalling in embryogenesis and tumourigenesis

Cited by 79 publications

References 117 publications

Nodal signalling and asymmetry of the nervous system

Nodal signalling and asymmetry of the nervous system

Evolution, divergence and loss of the Nodal signalling pathway: new data and a synthesis across the Bilateria

Activin/Nodal signalling in stem cells

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