FGF/MAPK signaling is required in the gastrula epiblast for avian neural crest induction

Stuhlmiller, Timothy J.; Garcı́a-Castro, Martı́n I.

doi:10.1242/dev.070276

Cited by 80 publications

(100 citation statements)

References 71 publications

(111 reference statements)

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“…Examination of NC markers at differentiation day 5 revealed decreased expression of all examined NC genes when PD 173074 was administered continuously for 5 days (Fig. 7B), suggesting that FGF signaling is required for human NC induction in accordance with previous findings from animal models (Stuhlmiller and Garcia-Castro, 2012b). WNT signaling is known to promote mesoderm induction in differentiating hESCs (Funa et al, 2015;Sumi et al, 2008).…”

Section: Human Neural Crest Induction Requires An Early and Balanced supporting

confidence: 88%

“…Endogenous FGF signaling is required for NC induction, and exogenous FGF triggers mesoderm character FGF signaling has been implicated in NC induction in animal models, either acting directly on NC precursors or via mesoderm induction (Mayor et al, 1997;Stuhlmiller and Garcia-Castro, 2012b;Yardley and Garcia-Castro, 2012). Treatment of differentiating hESCs with PD 173074, an FGFR1-and FGFR3-specific inhibitor, repressed the expression of the FGF targets SPRY1 and SPRY2 by 40-50% (Fig.…”

Section: Human Neural Crest Induction Requires An Early and Balanced mentioning

confidence: 98%

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WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

et al. 2016

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Neural crest (NC) cells arise early in vertebrate development, migrate extensively and contribute to a diverse array of ectodermal and mesenchymal derivatives. Previous models of NC formation suggested derivation from neuralized ectoderm, via meso-ectodermal, or neural-non-neural ectoderm interactions. Recent studies using bird and amphibian embryos suggest an earlier origin of NC, independent of neural and mesodermal tissues. Here, we set out to generate a model in which to decipher signaling and tissue interactions involved in human NC induction. Our novel human embryonic stem cell (ESC)-based model yields high proportions of multipotent NC cells (expressing SOX10, PAX7 and TFAP2A) in 5 days. We demonstrate a crucial role for WNT/β-catenin signaling in launching NC development, while blocking placodal and surface ectoderm fates. We provide evidence of the delicate temporal effects of BMP and FGF signaling, and find that NC development is separable from neural and/ or mesodermal contributions. We further substantiate the notion of a neural-independent origin of NC through PAX6 expression and knockdown studies. Finally, we identify a novel pre-neural border state characterized by early WNT/β-catenin signaling targets that displays distinct responses to BMP and FGF signaling from the traditional neural border genes. In summary, our work provides a fast and efficient protocol for human NC differentiation under signaling constraints similar to those identified in vivo in model organisms, and strengthens a framework for neural crest ontogeny that is separable from neural and mesodermal fates.

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Section: Human Neural Crest Induction Requires An Early and Balanced supporting

confidence: 88%

Section: Human Neural Crest Induction Requires An Early and Balanced mentioning

confidence: 98%

WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

et al. 2016

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“…FGFs have been shown to sensitize the dorsal ectoderm to respond to BMP inhibition, transcriptionally regulate BMPs and Wnts, and to contribute directly to NPB specification. 19,20,[54][55][56] In Xenopus, the DLMZ expresses a number of paracrine growth factors at the onset of gastrulation including wnt8, fgf4, fgf8, gdf6 and the BMP antagonist chordin (Fig. 2) and further expresses hairy2, fgfr1, fgfr4a, bmpr1a, pcns and ror2.…”

Section: Sources Of Wnt and Fgf Ligandsmentioning

confidence: 99%

Signaling pathways and tissue interactions in neural plate border formation

Schille

Schambony

2017

Neurogenesis

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The neural crest is a transient cell population that gives rise to various cell types of multiple tissues and organs in the vertebrate embryo. Neural crest cells arise from the neural plate border, a region localized at the lateral borders of the prospective neural plate. Temporally and spatially coordinated interaction with the adjacent tissues, the non-neural ectoderm, the neural plate and the prospective dorsolateral mesoderm, is required for neural plate border specification. Signaling molecules, namely BMP, Wnt and FGF ligands and corresponding antagonists are derived from these tissues and interact to induce the expression of neural plate border specific genes. The present mini-review focuses on the current understanding of how the NPB territory is formed and accentuates the need for coordinated interaction of BMP and Wnt signaling pathways and precise tissue communication that are required for the definition of the prospective NC in the competent ectoderm.

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“…We recently have shown that FGF signaling can modulate Pax7 in the early chick ectoderm (Stuhlmiller and García-Castro, 2012a;Yardley and García-Castro, 2012). Among putative effectors of FGF/ERK signaling are the ETS TFs.…”

Section: Discussionmentioning

confidence: 99%

“…This restricted expression offers a unique opportunity to advance our understanding of early events of NC formation. The expression of Pax7 has been analyzed in different contexts in various organisms, and it is known to be responsive to BMP, Wnt and FGF signals (Liem et al, 1997;Liem et al, 2000;Litingtung and Chiang, 2000;Briscoe et al, 2001;Basch et al, 2006;Otto et al, 2006;Maczkowiak et al, 2010;Stuhlmiller and García-Castro, 2012a). Analysis of mouse genomic sequences upstream of Pax7 identified a 10 kb region able to recapitulate endogenous Pax7 expression in only a few migratory cranial NC cells and the roof plate (Lang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pax7 is regulated by cMyb during early neural crest development through a novel enhancer

et al. 2013

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SUMMARYThe neural crest (NC) is a migratory population of cells unique to vertebrates that generates many diverse derivatives. NC cells arise during gastrulation at the neural plate border (NPB), which is later elevated as the neural folds (NFs) form and fuse in the dorsal region of the closed neural tube, from where NC cells emigrate. In chick embryos, Pax7 is an early marker, and necessary component of NC development. Unlike other early NPB markers, which are co-expressed in lateral ectoderm, medial neural plate or posterior-lateral mesoderm, Pax7 early expression seems more restricted to the NPB. However, the molecular mechanisms controlling early Pax7 expression remain poorly understood. Here, we identify a novel enhancer of Pax7 in avian embryos that replicates the expression of Pax7 associated with early NC development. Expression from this enhancer is found in early NPB, NFs and early emigrating NC, but unlike Pax7, which is also expressed in mesodermal derivatives, this enhancer is not active in somites. Further analysis demonstrates that cMyb is able to interact with this enhancer and modulates reporter and endogenous early Pax7 expression; thus, cMyb is identified as a novel regulator of Pax7 in early NC development. KEY WORDS: Neural plate border, Neural crest, PAX7, cMyb, Enhancer, ChickPax7 is regulated by cMyb during early neural crest development through a novel enhancerStephanie Vadasz, Jonathan Marquez, Maria Tulloch, Natalia A. Shylo and Martín I. García-Castro* DEVELOPMENT 3692 regulatory elements and TFs that initiate the expression of Pax7 at the NPB have not been reported.Here, we identify a novel Pax7 cis-regulatory element that directs expression in the avian NPB, NFs and early migrating NC cells, similar to the endogenous Pax7 expression associated with early NC. This element does not provide expression in later NC or in mesoderm, where endogenous Pax7 is seen. Through mutagenesis and overexpression studies, we unveil cMyb as a regulator of this enhancer and of endogenous early Pax7 expression. Our study is the first to demonstrate the ability of cMyb to regulate a border specifier directly during NC development and thus proposes a fundamental role for cMyb during the early phases of the NC-GRN. MATERIALS AND METHODS Sequence conservation and TF-binding analysisSequence conservation was determined using VISTA Browser (Visel et al., 2007), over a 50 bp window with 70% conserved identity. Putative TFbinding sites were identified using the JASPAR core vertebrate database (Bryne et al., 2008). Plasmid constructsEnhancer constructs were PCR amplified (DNeasy Kit, Qiagen) from genomic chick or human DNA (a gift from J. Noonan, New Haven, CT, USA), and cloned into ptkEGFP (a gift from H. Kondoh, Osaka, Japan) or ptkmCherry (a gift from D. Meulemans, Boulder, CO, USA) using KpnI and XhoI. pRFP was generated by removing the miRNA cassette from pRFPRNAi (ARK Genomics). Deletion constructs were generated by first amplifying each end with primers containing 15 bp of internal overlapping sequence fol...

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FGF/MAPK signaling is required in the gastrula epiblast for avian neural crest induction

Cited by 80 publications

References 71 publications

WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

Signaling pathways and tissue interactions in neural plate border formation

Pax7 is regulated by cMyb during early neural crest development through a novel enhancer

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