Developmental regulation of neurotrophin-3 and trk C splice variants in optic nerve glia in vivo.
Extensive evidence indicates that the survival and development of neurons is dependent on neurotrophins. However, the factors potentially required for glial development and function, and the sites of synthesis, are not well defined. To investigate the potential role of neurotrophins in glial development in vivo, we studied the trk family of receptors and their cognate neurotrophins in the postnatal rat optic nerve using reverse transcription-polymerase chain reaction. Our results indicate that trk A, B and C messenger RNAs are expressed throughout development, and in adulthood. Both trk B and trk C expression decreased during development. However, trk C expression decreased most markedly, reaching barely detectable levels by day 90. These findings suggest that neurotrophins can affect both immature and mature glial function and that their actions may be regulated through the modulation of putative receptors. To determine whether alternatively spliced forms of trk C potentially mediate neurotrophin-3 actions, we assessed expression of the different trk C isoforms. We employed reverse transcription-polymerase chain reaction using primers that selectively amplify the extracellular or intracellular domains. Optic nerve expressed both the full-length receptor and one form containing an insertion in the tyrosine kinase domain. In addition, the expression of the insert splice variant was developmentally regulated. Our observations suggest that, in glia, actions of neurotrophin-3 are probably mediated through the full-length receptor and that selected alternatively spliced forms may also be involved in trk C receptor function. To determine whether glia at different stages of differentiation elaborate neurotrophins, we analysed expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophins-3 and -4/5 in the optic nerve during development. Messenger RNAs for all the neurotrophins were detected at all postnatal ages, suggesting that progenitor cells, immature and mature glia are potential sources of neurotrophins. However, neurotrophin expression was not developmentally regulated. The invariant neurotrophin messenger RNA levels, and the changing expression of trk B and trk C during ontogeny, suggest that trophic regulation of glial development is primarily governed through modulation of receptor expression.
Elkabes
S
S
Neuroscience and Cell Biology, Robert W. Johnson Medical School, Piscataway, NJ 08854, USA.
Schaar
D G
DG
Dreyfus
C F
CF
Black
I B
IB
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D015870:Gene Expression; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects*; D009900:Optic Nerve / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases