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-beta2 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.