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.
Constam
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DB
University Hospital of Zürich, Department of Internal Medicine, Switzerland.
Schmid
P
P
Aguzzi
A
A
Schachner
M
M
Fontana
A
A
D000818:Animals; D001923:Brain Chemistry; D002455:Cell Division; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013234:Stem Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor