Biochemical and Biophysical Research Communications
PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral cortex
Section snippets
Materials and methods
Animals and surgery. Pregnant ddY mice were purchased from Japan SLC (Shizuoka, Japan), and handled according to the Guidelines of Experimental Animal Care issued by the Office of the Prime Minister of Japan. Surgery and manipulation of animals were performed as described [8], [11]. Briefly, pregnant mice carrying 13.5-day-old embryos (E13.5) were anesthetized with sodium pentobarbital (30 μg/g, i.p.), and their uterine horns were exposed. About 1 μl of phosphate-buffered saline (PBS) containing
Alteration of the position of cortical neurons by PACAP
We labeled the progenitors with BrdU 6 h after PACAP or vehicle administration on E13.5 and examined the distribution of the labeled cells at P6 with a confocal laser microscope (Fig. 1A). The greatest numbers of cellsBrdU+ were observed in sector nos. 6–7, corresponding to layer IV of the cerebral cortex, in the vehicle-injected animals (Fig. 1A,B). However, in the PACAP-treated animals, most of the cellsBrdU+ was localized in sector nos. 2–5, corresponding to layers V and VI (Fig. 1A,B). Thus
Discussion
In this study, we revealed that PACAP stimulated the phosphorylation of CREB of the embryonic cortical progenitors. We propose that phosphorylated CREB mediated the release of cortical progenitors from the cell cycle and altered the laminar fate of their daughter neurons, because both actions were completely blocked by PKA inhibitor co-administered with PACAP. Also, the PKA inhibitor behaved oppositely against PACAP actions on the cortical progenitors. Therefore, PKA/CREB signaling would be
Acknowledgment
This work was supported in part by grants from the programs Grants-in-Aid for Young Scientists (B; to H.F.) and Scientific Research (B; to S. F.) of the Japan Society for the Promotion of Science.
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