ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

Ellis, Pamela; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Katsumi; Ben-Haim, Nadav; Chen, Canhe; Dale, J. Kim; Shen, Michael M.; Constam, Daniel; Placzek, Marysia

doi:10.1242/dev.119628

Cited by 13 publications

(19 citation statements)

References 100 publications

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“…FGF signaling pathway plays a dominant role in embryonic development and is essential for ventral telencephalon development and digits formation [Li et al, 2005;Gutin et al, 2006;Ellis et al, 2015). FGF signaling is involved in maintaining Shh expression in the prechordal tissue, where it plays a crucial role in the induction of the ventral forebrain [Ellis et al, 2015]. FGFR1 also maintains expression of Shh in the developing limb [Li et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway

et al. 2016

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Holoprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high heterogeneity, both in clinics and genetics. We have developed a novel targeted next-generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway

et al. 2016

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“…1997;Dale et al, 1999;Ohyama et al, 2005;Hintze et al, 2017). PM, like notochord, expresses Shh (Patten et al, 2003;Ellis et al, 2015;Shimamura et al, 1995), and blockade or genetic ablation of Shh activity in the PM abrogates its ability to induce RDVM cells (Dale et al, 1997;Shimamura and Rubenstein, 1997;Patten et al, 2003;Geng et al, 2008;Aoto et al, 2009). Further, while mouse embryos in which Shh is conditionally deleted in the PM show cyclopia, those in which Shh is conditionally deleted in RDVM cells do not (Szabo et al, 2009).…”

Section: Shh Signaling In Anterior Regions Of the Neural Tubementioning

confidence: 99%

“…Nevertheless, exposure of neural tube explants to purified Shh protein revealed that Shh is not sufficient to induce RDVM cells. Instead, Shh acts co-operatively with the TGFb-ligand, Nodal, with which it is transiently expressed in the PM (Patten et al, 2003;Ellis et al, 2015). Loss-of-function studies in mouse and zebrafish, and analyses of human patients, suggest that a Shh-Nodal co-operation may be widely conserved and that Shh and Nodal signaling pathways are required cell-autonomously in RDVM cells (Mathieu et al, 2002;reviewed in (Placzek and Briscoe, 2005)).…”

Section: Shh Signaling In Anterior Regions Of the Neural Tubementioning

confidence: 99%

“…The transition from RDVM to proliferating hypothalamic progenitors appears to be mediated by the PM. During the time the PM is adjacent to RDVM cells, Shh/Nodal expression declines and BMP expression increases (Dale et al, 1999;Ellis et al, 2015). Exposure of RDVM explants to BMPs upregulates the transcriptional repressor, Tbx2 and the signaling factor, Fgf10.…”

Section: Shh Signaling In Anterior Regions Of the Neural Tubementioning

confidence: 99%

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Sonic hedgehog in vertebrate neural tube development

Placzek

Briscoe²

2018

Int. J. Dev. Biol.

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The formation and wiring of the vertebrate nervous system involves the spatially and temporally ordered production of diverse neuronal and glial subtypes that are molecularly and functionally distinct. The chick embryo has been the experimental model of choice for many of the studies that have led to our current understanding of this process, and has presaged and informed a wide range of complementary genetic studies, in particular in the mouse. The versatility and tractability of chick embryos means that it remains an important model system for many investigators in the field. Here we will focus on the role of Sonic hedgehog (Shh) signaling in coordinating the diversification, patterning, growth and differentiation of the vertebrate nervous system. We highlight how studies in chick led to the identification of the role Shh plays in the developing neural tube and how subsequent work, including studies in the chick and the mouse revealed details of the cell intrinsic programs controlling cell fate determination. We compare these mechanisms at different rostral-caudal positions along the neuraxis and discuss the particular experimental attributes of the chick that facilitated this work.

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“…Studies in chick and mouse indicate a likely mechanism for the transition of Shh +ive RDVM to Shh +ive /BMP7 +ive /Fgf10 +ive cells. After inducing Shh +ive RDVM cells, the PM down‐regulates Shh/Nodal , and up‐regulates BMP7 , which in turn induces its own expression (and that of T‐box transcriptional repressors, Tbx2/Tbx3, and BMP4 ) in RDVM cells . BMP, acting in a paracrine manner from the PM, or in a juxtacrine manner from RDVM cells, induces Fgf10 in RDVM cells .…”

Section: Anisotropic Growth Model Of Hypothalamic Developmentmentioning

confidence: 99%

Development of the basal hypothalamus through anisotropic growth

Pearson

Towers

et al. 2019

J Neuroendocrinology

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The adult hypothalamus is subdivided into distinct domains: pre‐optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh / Fgf10 ‐expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior‐ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh +ive and Fgf10 +ive progenitors form. We describe current understanding of the mechanisms that induce Shh +ive /Fgf10 +ive progenitors and begin to direct their differentiation to anterior‐ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the “anisotropic growth model”. We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.

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ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

Cited by 13 publications

References 100 publications

Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway

Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway

Sonic hedgehog in vertebrate neural tube development

Development of the basal hypothalamus through anisotropic growth

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