A2-Pancortins (Pancortin-3 and-4) are the dominant Pancortins during neocortical development

We have identified a novel mouse gene named pancortin that is expressed dom inantly in the mature cerebral cortex. This gene produces four different sp ecies of proteins, Pancortin-1-4, sharing a common region in the middle of their structure with two variations at the N-terminal (A1 or A2 part) and C -terminal (C1 or C2 part) sides, respectively. In the present study, we sho wed that expression of mRNAs for A2-Pancortins (Pancortin species that cont ain the A2 part, i.e., (Pancortin-3 and -4) is more dominant than that of m RNAs for A2-Pancortins (Pancortin species that contain the Al part, i.e., P ancortin-1 and -2) in the prenatal mouse cerebral neocortex, Using western blot analysis, we found that substantial amounts of both A2-Pancortins were present in the prenatal cerebral neocortex and P19 cells after inducing ne uronal differentiation. A2-Pancortins were still present in the cerebral ne ocortex of the adult, although their mRNAs were hardly detected. In contras t, the amount of A1-Pancortins did not increase after the third postnatal w eek in spite of their intense gene expression. Furthermore, we showed that recombinant Pancortin-3, one of the A2-Pancortins, was a secreted protein, in contrast to Pancortin-1 tone of the A1-Pancortins). These results sugges t that A2-Pancortins are extracellular proteins essential for neuronal diff erentiation and that their molecular behavior is distinct from that of Al-P ancortins.