In Choose Your Own Adventure books, readers make decisions that determine their character's fate. Similarly, in neuronal development, cell signaling events determine cellular identity. Endo et al. report that Notch signaling determines the identity of Drosophila olfactory receptor neurons (ORNs) in a recent article in Nature Neuroscience.
In the Drosophila olfactory sensory system, sensory units called sensilla in the antenna and maxillary palp each contain one to four ORNs. Each ORN expresses one of approximately 60 odorant receptors and projects to a specific glomerulus in the antennal lobe, which is the first relay in the brain for odorant information. The selection of both odorant receptors and glomerular targets defines ORN identity.
The authors used mosaic analysis with a repressible cell marker to determine that two ORNs located in the same sensillum were derived from the same precursor cell. One of the ORNs projected to the DM6, and the other projected to the DL4 glomerulus. In a screen for mutations that disrupted axon projections, the authors identified Drosophila in which both ORNs projected together to innervate DM6. They mapped the mutation to the mastermind gene, which encodes a nuclear protein that is important in Notch signaling. In Drosophila lacking the Notch antagonist Numb, the ORNs projected together to DL4. For each sensillum, the authors identified high- and low-Notch target glomeruli. Therefore, Notch signaling organized the projection path and glomerular target of ORN axons.
During development, Notch signaling mediates cell fate decisions. The authors determined that three rounds of cell divisions were necessary to generate ORNs from precursor cells. Half of the progeny from ORN precursor cells are non-neuronal, outer support cells, and the other half are inner neurons, half of which are positive for the protein Senseless. In mastermind knockouts, all of the daughter cells were Senseless-positive, suggesting that low levels of Notch signaling induce Senseless-positive inner neuron differentiation. In contrast, all of the inner neurons in numb knockout Drosophila were Senseless-negative, suggesting that high levels of Notch signaling induce Senseless-negative inner neuron differentiation. These data indicate a mechanism for the differentiation of high- and low-Notch ORNs in each sensillum.
Specific odorant receptors are expressed in high- and low-Notch ORNs. The authors drove expression of a reporter gene with promoters from six odorant receptors. In mastermind knockout Drosophila, Or46a and Or92a but not Or23a, Or43a, Or47a or Or71a promoters drove expression of the reporter gene. Conversely, in numb knockouts, Or23a, Or43a, Or47a and Or71a but not Or46a or Or92a promoters drove expression of the reporter gene.
Therefore Notch signaling defines and limits the set of olfactory genes that can be expressed in a given ORN, which subsequently defines the glomerulus an ORN will target. These data suggest that Notch simplifies the intricate organization of the olfactory sensory system in Drosophila.