Neurotrophin-3 influences the number and the laminar fate of cortical progenitors in the developing cerebral cortex of mice through the MEK/ERK1/2 signaling pathway.

The laminar formation in the developing cerebral cortex requires precisely regulated generation of phenotype-specific neurons. To determine whether neurotrophin-3 (NT3) is involved in this formation, we investigated the effects of NT3 administration in the telencephalic ventricular space on 13.5-day-old mouse embryos. NT3 increased the number of newly generated neurons and altered the neuronal phenotypes in the position and the transcription factors-expression profiles; the neuronal phenotypes originally committed for layer IV neurons were altered toward for layers II/III neurons. The former effects were observed when the parent progenitor cells were exposed to NT3 in the G1- to S-phase, whereas the latter effects were observed with exposure in the G1-phase. In addition, in vitro experiments revealed that the laminar fate alteration by NT3 was observed in the dissociated primary culture of cortical progenitors and the NT3 actions were suppressed by cotreatment with the MEK/ERK inhibitor. These observations suggest that NT3 is involved in the laminar formation of the developing cerebral cortex through the intercellular MEK/ERK pathway.