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 [1-3], whereas mice with a transgene causing high levels of Bcl-2 expression in the immune system show extended survival of B and T cells [4,5]. Overexpression of Bcl-2 in cultured neurons prevents their death following neurotrophin deprivation [6,7], and mice with a bcl-2 transgene under the control of a neuron-specific enolase promoter have increased numbers of neurons in several regions [8]. Cultured neurons expressing antisense bcl-2 RNA have an attenuated survival response to neurotrophins [9], and neurons of postnatal bcl-2-deficient mice die more rapidly following NGF deprivation in vitro [10] and are present in reduced numbers in vivo [11]. 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. (C) Current Biology Ltd ISSN 0960-9822.