Inter-axonal recognition organizes Drosophila olfactory map formation.

Olfactory systems across the animal kingdom show astonishing similarities in their morphological and functional organization. In mouse and Drosophila, olfactory sensory neurons are characterized by the selective expression of a single odorant receptor (OR) type and by the OR class-specific connection in the olfactory brain center. Monospecific OR expression in mouse provides each sensory neuron with a unique recognition identity underlying class-specific axon sorting into synaptic glomeruli. Here we show that in Drosophila, although OR genes are not involved in sensory neuron connectivity, afferent sorting via OR class-specific recognition defines a central mechanism of odortopic map formation. Sensory neurons mutant for the Ig-domain receptor Dscam converge into ectopic glomeruli with single OR class identity independent of their target cells. Mosaic analysis showed that Dscam prevents premature recognition among sensory axons of the same OR class. Single Dscam isoform expression in projecting axons revealed the importance of Dscam diversity for spatially restricted glomerular convergence. These data support a model in which the precise temporal-spatial regulation of Dscam activity controls class-specific axon sorting thereby indicating convergent evolution of olfactory map formation via self-patterning of sensory neurons.

Transcriptional regulation of peripheral glial cell differentiation in the embryonic nervous system of Drosophila.

The Drosophila nervous system is ideally suited to study glial cell development and function, because it harbors only relatively few glial cells, and nervous system development is very well conserved during evolution. In the past, enhancer trap studies provided tools allowing to study glial cells with a single-cell resolution and, moreover, disclosed a surprising molecular heterogeneity among the different glial cells. The peripheral nervous system in the embryo comprises only 12 glial cells in one hemisegment and thus offers a unique opportunity to decipher the mechanisms directing glial development. Here, we focus on transcriptional regulators that have been reported to function during gliogenesis. To uncover additional regulators, we have conducted a genetic screen and report the identification of two additional transcriptional regulators involved in the control of peripheral glial migration: nejire and tango.

Semaphorin-1a controls receptor neuron-specific axonal convergence in the primary olfactory center of Drosophila.

In the olfactory system of Drosophila, 50 functional classes of sensory receptor neurons (ORNs) project in a highly organized fashion into the CNS, where they sort out from one another and converge into distinct synaptic glomeruli. We identified the transmembrane molecule Semaphorin-1a (Sema-1a) as an essential component to ensure glomerulus-specific axon segregation. Removal of sema-1a in ORNs does not affect the pathfinding toward their target area but disrupts local axonal convergence into a single glomerulus, resulting in two distinct targeting phenotypes: axons either intermingle with adjacent ORN classes or segregate according to their odorant receptor identity into ectopic sites. Differential Sema-1a expression can be detected among neighboring glomeruli, and mosaic analyses show that sema-1a functions nonautonomously in ORN axon sorting. These findings provide insights into the mechanism by which afferent interactions lead to synaptic specificity in the olfactory system.

Notch and Numb are required for normal migration of peripheral glia in Drosophila.

A prominent feature of glial cells is their ability to migrate along axons to finally wrap and insulate them. In the embryonic Drosophila PNS, most glial cells are born in the CNS and have to migrate to reach their final destinations. To understand how migration of the peripheral glia is regulated, we have conducted a genetic screen looking for mutants that disrupt the normal glial pattern. Here we present an analysis of two of these mutants: Notch and numb. Complete loss of Notch function leads to an increase in the number of glial cells. Embryos hemizygous for the weak Notch(B-8X) allele display an irregular migration phenotype and mutant glial cells show an increased formation of filopodia-like structures. A similar phenotype occurs in embryos carrying the Notch(ts1) allele when shifted to the restrictive temperature during the glial cell migration phase, suggesting that Notch must be activated during glial migration. This is corroborated by the fact that cell-specific reduction of Notch activity in glial cells by directed numb expression also results in similar migration phenotypes. Since the glial migration phenotypes of Notch and numb mutants resemble each other, our data support a model where the precise temporal and quantitative regulation of Numb and Notch activity is not only required during fate decisions but also later during glial differentiation and migration.