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

Daniel B. Constam, Peter Schmid, Adriano Aguzzi, Melitta Camartin, Adriano Fontana

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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.

Original languageEnglish (US)
Pages (from-to)766-778
Number of pages13
JournalEuropean Journal of Neuroscience
Volume6
Issue number5
DOIs
StatePublished - Jan 1 1994

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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