Glial cells are increased proportionally in transgenic optic nerves with increased numbers of axons.
To study how an increase in axon number influences the number of glial cells in the mammalian optic nerve, we have analyzed a previously described transgenic mouse that expresses the human bcl-2 gene from a neuron-specific enolase promoter. In these mice, the normal postnatal loss of retinal ganglion cell axons is greatly decreased and, as a consequence, the number of axons in the optic nerve is increased by approximately 80% compared with wild-type mice. Remarkably, the numbers of oligodendrocytes, astrocytes, and microglial cells are all increased proportionally in the transgenic optic nerve. The increase in oligodendrocytes apparently results from both a decrease in normal oligodendrocyte death and an increase in oligodendrocyte precursor cell proliferation, whereas the increase in astrocytes apparently results from an increase in the proliferation of astrocyte lineage cells. Unexpectedly, the transgene is expressed in oligodendrocytes and astrocytes, but this does not seem to be responsible for the increased numbers of these cells. These findings indicate that developing neurons and glial cells can interact to adjust glial cell numbers appropriately when neuronal numbers are increased. We also show that the expression of the bcl-2 transgene in retinal ganglion cells protects the cell body from programmed cell death when the axon is cut, but it does not protect the isolated axon from Wallerian degeneration, even though the transgene-encoded protein is present in the axon.
Burne
J F
JF
Medical Research Council Developmental Neurobiology Programme, MRC Laboratory for Molecular Cell Biology, University College London, United Kingdom.
Staple
J K
JK
Raff
M C
MC
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001369:Axons / Q000502:physiology*; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology; D009410:Nerve Degeneration / Q000502:physiology; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology; D009900:Optic Nerve / Q000166:cytology* / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012165:Retinal Ganglion Cells / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2