A correction for this article has been published in Neural Development 2008, 3:31

Research article

FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development

Ugo Borello¹ , Inma Cobos^1,3 , Jason E Long^1,4 , Cornelis Murre² and John LR Rubenstein¹

¹Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143, USA

²Department of Biology, University of California, San Diego, CA 92093, USA

³ICREA and Department of Cell Biology, University of Barcelona. Avda. Diagonal, 08028 Barcelona, Spain

⁴Genentech, Inc., DNA Way, South San Francisco, CA 94080, USA

author email corresponding author email

Neural Development 2008, 3:17doi:10.1186/1749-8104-3-17

Published:	14 July 2008

Abstract

Background

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 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.

Results

Using 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.

Conclusion

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