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PreviousNext
Cover ArticleArticles, Development/Plasticity/Repair

The Indirect Role of Fibroblast Growth Factor-8 in Defining Neurogenic Niches of the Olfactory/GnRH Systems

Paolo Emanuele Forni, Kapil Bharti, Ellen M. Flannery, Tomomi Shimogori and Susan Wray
Journal of Neuroscience 11 December 2013, 33 (50) 19620-19634; https://doi.org/10.1523/JNEUROSCI.3238-13.2013
Paolo Emanuele Forni
1Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke,
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Kapil Bharti
2Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, and
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Ellen M. Flannery
1Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke,
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Tomomi Shimogori
3Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan
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Susan Wray
1Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke,
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Abstract

Bone morphogenic protein-4 (BMP4) and fibroblast growth factor-8 (FGF8) are thought to have opposite roles in defining epithelial versus neurogenic fate in the developing olfactory/vomeronasal system. In particular, FGF8 has been implicated in specification of olfactory and gonadotropin releasing hormone-1 (GnRH) neurons, as well as in controlling olfactory stem cell survival. Using different knock-in mouse lines and Cre-lox-mediated lineage tracing, Fgf8 expression and cell lineage was analyzed in the developing nose in relation to the expression of Bmp4 and its antagonist Noggin (Nog). FGF8 is expressed by cells that acquire an epidermal, respiratory cell fate and not by stem cells that acquire neuronal olfactory or vomeronasal cell fate. Ectodermal and mesenchymal sources of BMP4 control the expression of BMP/TGFβ antagonist Nog, whereas mesenchymal sources of Nog define the neurogenic borders of the olfactory pit. Fgf8 hypomorph mouse models, Fgf8neo/neo and Fgf8neo/null, displayed severe craniofacial defects together with overlapping defects in the olfactory pit including (1) lack of neuronal formation ventrally, where GnRH neurons normally form, and (2) altered expression of Bmp4 and Nog, with Nog ectopically expressed in the nasal mesenchyme and no longer defining the GnRH and vomeronasal neurogenic border. Together our data show that (1) FGF8 is not sufficient to induce ectodermal progenitors of the olfactory pit to acquire neural fate and (2) altered neurogenesis and lack of GnRH neuron specification after chronically reduced Fgf8 expression reflected dysgenesis of the nasal region and loss of a specific neurogenic permissive milieu that was defined by mesenchymal signals.

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The Journal of Neuroscience: 33 (50)
Journal of Neuroscience
Vol. 33, Issue 50
11 Dec 2013
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The Indirect Role of Fibroblast Growth Factor-8 in Defining Neurogenic Niches of the Olfactory/GnRH Systems
Paolo Emanuele Forni, Kapil Bharti, Ellen M. Flannery, Tomomi Shimogori, Susan Wray
Journal of Neuroscience 11 December 2013, 33 (50) 19620-19634; DOI: 10.1523/JNEUROSCI.3238-13.2013

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The Indirect Role of Fibroblast Growth Factor-8 in Defining Neurogenic Niches of the Olfactory/GnRH Systems
Paolo Emanuele Forni, Kapil Bharti, Ellen M. Flannery, Tomomi Shimogori, Susan Wray
Journal of Neuroscience 11 December 2013, 33 (50) 19620-19634; DOI: 10.1523/JNEUROSCI.3238-13.2013
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