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 co-treatment 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.