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 regulate developmental processes since they are distinctly expressed during embryogenesis and exert pleiotropic effects on cell growth and differentiation. In the present study the expression of TGF-beta isoforms was investigated in the postnatal and adult mouse brain. As shown by in situ hybridization, TGF-beta(2) was expressed in the choroid plexus, hippocampus, dentate gyrus and cerebellar Purkinje neurons, both postnatally and in adults. Furthermore, TGF-beta(2) expression was observed postnatally in immature cerebellar neurons of both the external and internal granule cell layers. In the external granule cell layer, the frequency of TGF-beta(2) transcripts increased until postnatal day 10 and 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. The significance of TGF-beta(2) production by cerebellar granule cells was further investigated using cultures of small cerebellar neurons. In these cultures reverse polymerase chain reaction analysis revealed expression of TGF-beta(2) but low or almost undetectable levels of TGF-beta(1) or -beta(3) mRNAs. Likewise, only TGF-beta(2) protein in its latent form was identified in the culture supernatant; the release of TGF-beta(2) was maximal during the second day in vitro. Furthermore, TGF-beta was found to inhibit the proliferation of cultured small cerebellar neurons. Taken together, these data suggest that TGF-beta(2) is involved in the regulation of postnatal development of the cerebellum.