TRANSIENT PRODUCTION OF TGF-BETA(2) BY POSTNATAL CEREBELLAR NEURONS AND ITS EFFECT ON NEUROBLAST PROLIFERATION

The beta transforming growth factors (TGF-beta) are suggested to regul ate developmental processes since they are distinctly expressed during embryogenesis and exert pleiotropic effects on cell growth and differ entiation. In the present study the expression of TGF-beta isoforms wa s investigated in the postnatal and adult mouse brain. As shown by in situ hybridization, TGF-beta(2) was expressed in the choroid plexus, h ippocampus, dentate gyrus and cerebellar Purkinje neurons, both postna tally and in adults. Furthermore, TGF-beta(2) expression was observed postnatally in immature cerebellar neurons of both the external and in ternal granule cell layers. In the external granule cell layer, the fr equency of TGF-beta(2) transcripts increased until postnatal day 10 an d declined thereafter. In contrast to TGF-beta(2), no TGF-beta(1) mRNA was detected in cerebellar granule cells. TGF-beta(3) expression was widely distributed in postnatal brains although at very low levels. Th e significance of TGF-beta(2) production by cerebellar granule cells w as further investigated using cultures of small cerebellar neurons. In these cultures reverse polymerase chain reaction analysis revealed ex pression of TGF-beta(2) but low or almost undetectable levels of TGF-b eta(1) or -beta(3) mRNAs. Likewise, only TGF-beta(2) protein in its la tent form was identified in the culture supernatant; the release of TG F-beta(2) was maximal during the second day in vitro. Furthermore, TGF -beta was found to inhibit the proliferation of cultured small cerebel lar neurons. Taken together, these data suggest that TGF-beta(2) is in volved in the regulation of postnatal development of the cerebellum.