Mechanisms that guide adult neural stem cells towards a specific neuronal fate in the brain are largely unknown. Studying the adult olfactory system Hack and his colleagues have explored the role of two transcription factors expressed in the subependymal zone in the adulthood but not during development: PAX6 and OLIG2 (Neuronal fate determinants of adult olfactory bulb neurogenesis. Nature Neuroscience on-line publication doi:10.1038/nn1479, 2005).

Apparently unique in the nervous system, olfactory receptor neurones are continually replaced throughout life by differentiation of stem cells in the olfactory mucosa. The principal neurones in the olfactory bulb are the mitral and tufted cells: their axons form its output via the olfactory tract. The main types of intrinsic neurone in the olfactory bulb are periglomerular cells and granule cells. The majority of periglomerular cells are dopaminergic; some are GABA-ergic. Granule cells, similar in size to periglomerular cells, are characterized by the absence of an axon, resembling amacrine cells in the retina. These “olfactory amacrine cells” are exclusively GABA-ergic.

In the adulthood, these cells are specified during their migration from the subependymal zone to the olfactory bulb.

The authors showed an important role of PAX6 and OLIG2 during the migration-differentiation process in the adult neuronal regeneration in the olfactory system. PAX6 specifically promotes the neurogenesis of periglomerular dopaminergic neurons, which are abnormally regulated in Parkinson’s disease.


BM&L-September 2005