Primary neurons in the mammalian olfactory epithelium are continuously renewed, even during adulthood. According to Bauer et al., writing in The Journal of Neuroscience, leukaemia inhibitory factor (LIF) is the key to this neurogenesis, and is produced by dying neurons to stimulate their replacement.

The left image is an in situ hybridization for olfactory marker protein, illustrating the location of the olfactory neurons in the epithelium. The right image is an in situ RT-PCR for leukaemia inhibitory factor (LIF), showing that olfactory neurons are positive for LIF mRNA after olfactory bulb ablation. Courtesy of P. H. Patterson, California Institute of Technology, Pasadena, California.

LIF is a cytokine that is involved in regulating the differentiation of many cells, and is one of many factors that has been shown to stimulate the production of new olfactory neurons from their progenitors in vitro. Bauer et al. studied mice in which the olfactory bulbs had been ablated, leading to massive cell death in the olfactory epithelium followed by a wave of mitosis in the globose basal cells (which give rise to the olfactory neurons). When they examined the olfactory epithelium after this injury, they found that LIF was strongly induced. The LIF receptor is also upregulated during this period, but the authors found no other cytokines or growth factors that showed this pattern of upregulation. LIF was induced in the neurons of the olfactory epithelium — the population of neurons that dies through apoptosis after olfactory bulb ablation.

To find out whether LIF is needed for the production of new olfactory neurons after injury, the authors used LIF knockout mice. In these mice, ablation of the olfactory bulb still led to apoptosis in the olfactory epithelium, but there was no increase in progenitor cell division. Finally, Bauer et al. induced overexpression of LIF in the olfactory epithelium of unlesioned mice using an adenoviral vector, and found that this caused increased neurogenesis in the apical olfactory epithelium.

Although there are a number of questions to be answered, the authors propose that LIF is released by dying olfactory neurons to stimulate their replacement through cell division. It will be interesting to see whether similar factors can be identified in other neuronal populations that have been reported to be replaced after apoptosis. If so, it could have important implications for brain repair.