FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development

<p>Abstract</p> <p>Background</p> <p>Growth, differentiation and regional specification of telencephalic domains, such as the cerebral cortex, are regulated by the interplay of secreted proteins produced by patterning centers and signal transduction systems deployed in...

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Main Authors: Long Jason E, Cobos Inma, Borello Ugo, Murre Cornelis, Rubenstein John LR
Format: Article
Language:English
Published: BMC 2008-07-01
Series:Neural Development
Online Access:http://www.neuraldevelopment.com/content/3/1/17
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author Long Jason E
Cobos Inma
Borello Ugo
Murre Cornelis
Rubenstein John LR
author_facet Long Jason E
Cobos Inma
Borello Ugo
Murre Cornelis
Rubenstein John LR
author_sort Long Jason E
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Growth, differentiation and regional specification of telencephalic domains, such as the cerebral cortex, are regulated by the interplay of secreted proteins produced by patterning centers and signal transduction systems deployed in the surrounding neuroepithelium. Among other signaling molecules, members of the fibroblast growth factor (FGF) family have a prominent role in regulating growth, differentiation and regional specification. In the mouse telencephalon the rostral patterning center expresses members of the <it>Fgf </it>family (<it>Fgf8</it>, <it>Fgf15</it>, <it>Fgf17</it>, <it>Fgf18</it>). FGF8 and FGF17 signaling have major roles in specification and morphogenesis of the rostroventral telencephalon, whereas the functions of FGF15 and FGF18 in the rostral patterning center have not been established.</p> <p>Results</p> <p>Using <it>Fgf15</it><sup>-/- </sup>mutant mice, we provide evidence that FGF15 suppresses proliferation, and that it promotes differentiation, expression of <it>CoupTF1 </it>and caudoventral fate; thus, reducing <it>Fgf15 </it>and <it>Fgf8 </it>dosage have opposite effects. Furthermore, we show that FGF15 and FGF8 differentially phosphorylate ERK (p42/44), AKT and S6 in cultures of embryonic cortex. Finally, we show that FGF15 inhibits proliferation in cortical cultures.</p> <p>Conclusion</p> <p>FGF15 and FGF8 have distinct signaling properties, and opposite effects on neocortical patterning and differentiation; FGF15 promotes <it>CoupTF1 </it>expression, represses proliferation and promotes neural differentiation.</p>
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spelling doaj.art-b8ff8f88f3714bb58a647ffa2fb63ea22022-12-22T03:10:19ZengBMCNeural Development1749-81042008-07-01311710.1186/1749-8104-3-17FGF15 promotes neurogenesis and opposes FGF8 function during neocortical developmentLong Jason ECobos InmaBorello UgoMurre CornelisRubenstein John LR<p>Abstract</p> <p>Background</p> <p>Growth, differentiation and regional specification of telencephalic domains, such as the cerebral cortex, are regulated by the interplay of secreted proteins produced by patterning centers and signal transduction systems deployed in the surrounding neuroepithelium. Among other signaling molecules, members of the fibroblast growth factor (FGF) family have a prominent role in regulating growth, differentiation and regional specification. In the mouse telencephalon the rostral patterning center expresses members of the <it>Fgf </it>family (<it>Fgf8</it>, <it>Fgf15</it>, <it>Fgf17</it>, <it>Fgf18</it>). FGF8 and FGF17 signaling have major roles in specification and morphogenesis of the rostroventral telencephalon, whereas the functions of FGF15 and FGF18 in the rostral patterning center have not been established.</p> <p>Results</p> <p>Using <it>Fgf15</it><sup>-/- </sup>mutant mice, we provide evidence that FGF15 suppresses proliferation, and that it promotes differentiation, expression of <it>CoupTF1 </it>and caudoventral fate; thus, reducing <it>Fgf15 </it>and <it>Fgf8 </it>dosage have opposite effects. Furthermore, we show that FGF15 and FGF8 differentially phosphorylate ERK (p42/44), AKT and S6 in cultures of embryonic cortex. Finally, we show that FGF15 inhibits proliferation in cortical cultures.</p> <p>Conclusion</p> <p>FGF15 and FGF8 have distinct signaling properties, and opposite effects on neocortical patterning and differentiation; FGF15 promotes <it>CoupTF1 </it>expression, represses proliferation and promotes neural differentiation.</p>http://www.neuraldevelopment.com/content/3/1/17
spellingShingle Long Jason E
Cobos Inma
Borello Ugo
Murre Cornelis
Rubenstein John LR
FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
Neural Development
title FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
title_full FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
title_fullStr FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
title_full_unstemmed FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
title_short FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development
title_sort fgf15 promotes neurogenesis and opposes fgf8 function during neocortical development
url http://www.neuraldevelopment.com/content/3/1/17
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AT borellougo fgf15promotesneurogenesisandopposesfgf8functionduringneocorticaldevelopment
AT murrecornelis fgf15promotesneurogenesisandopposesfgf8functionduringneocorticaldevelopment
AT rubensteinjohnlr fgf15promotesneurogenesisandopposesfgf8functionduringneocorticaldevelopment