FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development.

Area of Science:

• Developmental neurobiology
• Molecular signaling pathways
• Cerebral cortex development

Background:

• Telencephalic development relies on secreted proteins from patterning centers.
• Fibroblast growth factors (FGFs) are key regulators of neural growth and differentiation.
• The rostral patterning center expresses FGF8, FGF15, FGF17, and FGF18, with FGF8 and FGF17 roles established, but FGF15 and FGF18 functions unclear.

Purpose of the Study:

• To investigate the role of FGF15 in the rostral patterning center of the mouse telencephalon.
• To elucidate the distinct functions of FGF15 compared to FGF8 in cortical development.

Main Methods:

• Utilized Fgf15 knockout (Fgf15-/-) mutant mice.
• Analyzed proliferation and differentiation markers in embryonic cortex cultures.
• Examined differential phosphorylation of ERK, AKT, and S6 by FGF15 and FGF8.

Main Results:

• FGF15 suppresses proliferation and promotes differentiation, CoupTF1 expression, and caudoventral fate.
• FGF15 and FGF8 exhibit differential effects on ERK, AKT, and S6 phosphorylation.
• FGF15 was shown to inhibit proliferation in cortical cell cultures.

Conclusions:

• FGF15 and FGF8 possess distinct signaling properties and opposing effects on neocortical patterning and differentiation.
• FGF15 promotes CoupTF1 expression, inhibits proliferation, and drives neural differentiation.
• These findings clarify the specific roles of FGF15 in early brain development.