Complex and dynamic patterns of Wnt pathway gene expression in the developing chick forebrain

Quinlan, Robyn; Graf, Manuela; Mason, Ivor; Lumsden, Andrew; Kiecker, Clemens

doi:10.1186/1749-8104-4-35

Cited by 54 publications

(57 citation statements)

References 168 publications

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“…Axud1 has been proposed to be a Wnt target gene based on studies in cell lines and chick embryos(Ishiguro et al, 2001; Quinlan et al, 2009). Therefore, we tested the hypothesis that Axud1 is downstream of Wnt signaling in the dorsal neural folds.…”

Section: Resultsmentioning

confidence: 99%

Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation

2015

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Summary Neural crest cells are induced at the neural plate border by the combined action of transcription factors and signaling molecules. Here, we show that Axud1, a downstream effector of Wnt signaling, represents a critical missing link that integrates signaling and transcriptional cues to mediate neural crest formation. Axud1 is a transcription factor expressed in neural crest progenitors in a Wnt1/β-catenin dependent manner. Axud1 loss leads to downregulation of multiple genes involved in neural crest specification, similar to the effects of Wnt1 knockdown. Importantly, Axud1 is sufficient to rescue neural crest formation after disruption of Wnt signaling. Furthermore, it physically interacts with neural plate border genes Pax7 and Msx1 in vivo to directly activate transcription of stem cell factor FoxD3, initiating the neural crest program. Thus, Axud1 integrates Wnt signaling with transcriptional inputs to endow the neural crest with its unique molecular signature.

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Section: Resultsmentioning

confidence: 99%

Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation

2015

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“…The Wnt signalling pathway directs dorsal cell fate decisions during embryonic development (reviewed by Klaus and Birchmeier, 2008). Therefore, we next studied the expression patterns of various Wnt family members, such as Wnt2b, Wnt3a and Wnt8b (see also GarciaLopez et al, 2004;Rossi et al, 2007;Quinlan et al, 2009;Van Raay and Vetter, 2004). Of the analysed Wnt ligands, only Wnt2b transcripts were restricted to the dorsal surface ectoderm and dorsal ov at the time the RPE is specified (Fig.…”

Section: Molecular Signals Involved In Optic Vesicle Patterningmentioning

confidence: 99%

RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling

Steinfeld

Coronato

et al. 2013

Development

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The retinal pigment epithelium (RPE) is indispensable for vertebrate eye development and vision. In the classical model of optic vesicle patterning, the surface ectoderm produces fibroblast growth factors (FGFs) that specify the neural retina (NR) distally, whereas TGFβ family members released from the proximal mesenchyme are involved in RPE specification. However, we previously proposed that bone morphogenetic proteins (BMPs) released from the surface ectoderm are essential for RPE specification in chick. We now show that the BMP-and Wnt-expressing surface ectoderm is required for RPE specification. We reveal that Wnt signalling from the overlying surface ectoderm is involved in restricting BMP-mediated RPE specification to the dorsal optic vesicle. Wnt2b is expressed in the dorsal surface ectoderm and subsequently in dorsal optic vesicle cells. Activation of Wnt signalling by implanting Wnt3a-soaked beads or inhibiting GSK3β at optic vesicle stages inhibits NR development and converts the entire optic vesicle into RPE. Surface ectoderm removal at early optic vesicle stages or inhibition of Wnt, but not Wnt/β-catenin, signalling prevents pigmentation and downregulates the RPE regulatory gene Mitf. Activation of BMP or Wnt signalling can replace the surface ectoderm to rescue MITF expression and optic cup formation. We provide evidence that BMPs and Wnts cooperate via a GSK3β-dependent but β-catenin-independent pathway at the level of pSmad to ensure RPE specification in dorsal optic vesicle cells. We propose a new dorsoventral model of optic vesicle patterning, whereby initially surface ectoderm-derived Wnt signalling directs dorsal optic vesicle cells to develop into RPE through a stabilising effect of BMP signalling.

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“…At the stage of the early germinal neuroepithelium, Wnt genes and Wnt pathway modulators are expressed in overlapping spatial and temporal patterns [62,63,64] and are critical for establishing signaling centers that inform regional identities along the rostral-caudal and dorsal-ventral axes of the developing CNS [65,66,67](Table 2). Structural and functional impairments in the forebrain (derived from telencephalon and diencephalon), midbrain (derived from mesencephalon), and hindbrain (derived from metencephalon and myelencephalon) have all been associated with neuropsychiatric pathogenesis [68,69,70].…”

Section: Brain Regionalizationmentioning

confidence: 99%

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

Mulligan

Cheyette

2016

Complex Psychiatry

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Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions. Simultaneously, large-scale human genomic studies are providing evidence that sequence variation in Wnt signal pathway genes contributes to pathogenesis in several psychiatric disorders. This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.

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Complex and dynamic patterns of Wnt pathway gene expression in the developing chick forebrain

Cited by 54 publications

References 168 publications

Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation

Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation

RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

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