Temporal patterns of olfactory bulb interneuron neurogenesis.

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see Interneurons are among the most diverse cell populations in the CNS, exhibiting a wide range of morphological, physiological , and molecular properties. Efforts to describe the origins of interneuron diversity have produced varying degrees of success in the spinal cord and cerebral cortex, but have proven more elusive in the olfac-tory bulb, where new interneurons are integrated during both embryogenesis and adulthood. To date, the most successful attempts to discover the origins of inter-neuron subtypes have involved birthdat-ing techniques and genetic manipulations using interneuron-specific transcription factors. Recent efforts to determine specific spatial and temporal origins of distinct interneuron subtypes have helped develop a model in which interneuron diversity arises not from one homogeneous progenitor pool, but rather from a mosaic of spatially and temporally restricted progenitors , each contributing to a different interneuron subtype population. Until recently, analyses of the origins of olfactory bulb interneuron subtypes were limited to profiling transcription factors that define specific interneuron populations. Molecular specification of different subtypes occurs early in development in the dorsal lateral ganglionic eminence , where embryonic olfactory bulb interneurons originate, and continues later in the subventricular zone, the birthplace of adult olfactory bulb interneurons. There are at least 10 known transcription factors associated with olfactory bulb in-terneuron specification (for a complete review, see Bovetti et al., 2007). For example , GABAergic and dopaminergic phenotypes are specified by the transcription factors Dlx1, Dlx2, Dlx5, and Dlx6. Additionally , the transcription factor Pax6 regulates the differentiation of periglomeru-lar cells and superficial granule cells that are dopaminergic or tyrosine hydroxylase (TH)-positive. Merkle et al. (2007) added to this picture of olfactory bulb interneuron diversity by showing that different interneuron subtypes are specified in spatially distinct subregions within the subventricular zone. By labeling targeted, spatially confined radial glial progenitor cells at post-natal day 0 (P0), the authors showed that interneuron subtype production is determined by unique, regionally specific progenitor pools. Importantly, because the progenitors (not migrating neuroblasts) were targeted directly, this study demonstrated that there is a tremendous degree of heterogeneity in the subventricular zone itself, before neurons become postmitotic. The recent study by Batista-Brito …