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Transient Production of TGF-β2 by Postnatal Cerebellar Neurons and its Effect on Neuroblast Proliferation

Authors


Daniel B. Constam, as above

Abstract

The beta transforming growth factors (TGF-β) 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-β isoforms was investigated in the postnatal and adult mouse brain. As shown by in situ hybridization, TGF-β2 was expressed in the choroid plexus, hippocampus, dentate gyrus and cerebellar Purkinje neurons, both postnatally and in adults. Furthermore, TGF-β2 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-β2 transcripts increased until postnatal day 10 and declined thereafter. In contrast to TGF-β2, no TGF-β1 mRNA was detected in cerebellar granule cells. TGF-β3 expression was widely distributed in postnatal brains although at very low levels. The significance of TGF-β2 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-β2 but low or almost undetectable levels of TGF-β1 or -β3 mRNAs. Likewise, only TGF-β2 protein in its latent form was identified in the culture supernatant; the release of TGF-β2 was maximal during the second day in vitro. Furthermore, TGF-β was found to inhibit the proliferation of cultured small cerebellar neurons. Taken together, these data suggest that TGF-β2 is involved in the regulation of postnatal development of the cerebellum.

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