Bcl-2 influences axonal growth rate in embryonic sensory neurons.
Bcl-2 plays a key role in regulating cell survival in the immune and nervous systems. Mice lacking the bcl-2 gene have markedly reduced numbers of B and T cells as a result of increased apoptosis, whereas mice with a transgene causing high levels of Bcl-2 expression in the immune system show extended survival of B and T cells. Overexpression of Bcl-2 in cultured neurons prevents their death following neurotrophin deprivation, and mice with a bcl-2 transgene under the control of a neuron-specific enolase promoter have increased numbers of neurons in several regions. Cultured neurons expressing antisense bcl-2 RNA have an attenuated survival response to neurotrophins, and neurons of postnatal bcl-2-deficient mice die more rapidly following NGF deprivation in vitro and are present in reduced numbers in vivo. Here, we show that Bcl-2 also plays a role in regulating axonal growth rates in embryonic neurons. Sensory neurons from the trigeminal ganglia of bcl-2-deficient mouse embryos, removed from the embryo on embryonic day 11 or 12, extend axons more slowly in vitro than do neurons from wild-type embryos of the same age. Serial measurements of axonal length in the same neurons revealed that there were marked differences in axonal growth rate between bcl-2-deficient and wild-type neurons, irrespective of whether the neurons were grown with nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3. Because there was no significant difference in the numbers of wild-type and bcl-2-deficient neurons surviving with each neurotrophin at this early stage of development, the effect of Bcl-2 on axonal growth rate is not a consequence of its well documented role in preventing apoptosis.
Hilton
M
M
School of Biological and Medical Sciences, University of St. Andrews, Fife, UK.
Middleton
G
G
Davies
A M
AM
D000818:Animals; D001369:Axons; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D019253:Proto-Oncogene Proteins c-bcl-2