, 2000 and Simpson et al., 2000). This “Robo code” was an early demonstration of how combinatorial signaling can organize a developing nervous system. In Drosophila, each class of sensory neuron sends axons that terminate at a specific region within the developing VNC. The Bate lab (Cambridge, UK) discovered that sensory axons that project along

the mediolateral axis of the VNC use Robo to respond to the same-midline-derived gradient of http://www.selleckchem.com/products/ABT-263.html Slit that organizes the longitudinal tracts ( Zlatic et al., 2003). To gain their correct position along the dorsoventral axis, however, they are guided by a Plexin-mediated response to gradients of Semaphorins ( Zlatic et al., 2009). Thus, the three-dimensional topography of sensory neuron projections is mediated by two orthogonally oriented chemorepulsive gradients. Zlatic et al. (2009) also showed that mechanosensory axons from the chordotonal organ preferentially grow

toward and selectively fasciculate with the intermediate Fas2-expressing tract. Homophilic Fas2 adhesion cannot account for this specificity, however, as the ch axons are not themselves Fas2 positive. Instead, ch axons are guided to that location by Semaphorin signaling. Consistent with this observation, only the intermediate tract and the ch axon projections are disrupted in PlexB

mutants. Wu et al. (2011) selleck kinase inhibitor have extended this result at the cellular and molecular level, demonstrating that guidance depends Cell press on the coordinate response of the ch neurons and the intermediate fascicle axons to the two secreted semaphorins, Sema-2a and Sema-2b. Both Sema-2a and Sema-2b have been proposed as ligands for the PlexB receptor. The authors show convincingly that both molecules do indeed signal in this system through PlexB: mutants of either semaphorin gene alone do not fully recapitulate the PlexB phenotype, but double mutants do. The authors further demonstrate that the two Semaphorins have opposite effects in this system. Sema-2b acts as an attractive cue while Sema-2a acts as a chemorepellant. Together, they confine ch axons and their targets to the correct neuropilar region. The authors began to crack the combinatorial Sema-2 code by examining the complexities of Sema-2-PlexB signaling. In particular, Sema-2b expression is strongest on the intermediate tract, and fasciculation phenotypes were rescued by selective expression of either normal or a membrane-tethered Sema-2b in those cells. This shows that Sema-2b both attracts innervating axons and enhances fasciculation over a short range, perhaps through direct contact.