FGF15 promotes neurogenesis and opposes FGF8 function during neocortical developmentReportar como inadecuado




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Neural Development

, 3:17

First Online: 14 July 2008Received: 02 May 2008Accepted: 14 July 2008

Abstract

BackgroundGrowth, 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 Fgf family Fgf8, Fgf15, Fgf17, Fgf18. 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.

ResultsUsing Fgf15 mutant mice, we provide evidence that FGF15 suppresses proliferation, and that it promotes differentiation, expression of CoupTF1 and caudoventral fate; thus, reducing Fgf15 and Fgf8 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.

ConclusionFGF15 and FGF8 have distinct signaling properties, and opposite effects on neocortical patterning and differentiation; FGF15 promotes CoupTF1 expression, represses proliferation and promotes neural differentiation.

AbbreviationsBMPbone morphogenetic protein

BrdUbromo-deoxyuridine

CGEcaudal ganglionic eminence

DMEMDulbecco-s modified Eagle-s medium

Eembryonic day

FBSfetal bovine serum

FGFfibroblast growth factor

FGFRFGF receptor

IdUiodo-deoxyuridine

MAPKmitogen activated protein kinase

PH3phospho-histone H3

PSBpallium-subpallium boundary

SHHsonic hedgehog

SVZsubventricular zone

VZventricular zone.

Electronic supplementary materialThe online version of this article doi:10.1186-1749-8104-3-17 contains supplementary material, which is available to authorized users.

An erratum to this article is available at http:-dx.doi.org-10.1186-1749-8104-3-31.

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Autor: Ugo Borello - Inma Cobos - Jason E Long - Cornelis Murre - John LR Rubenstein

Fuente: https://link.springer.com/



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