Not surprisingly, chemotropism is complex:

the same ligand can be either attractive or repulsive depending on the receptor complexes expressed by the growth cone. Axons, in turn, usually express several guidance receptors. The combination of multiple guidance cues and receptors effectively constitutes a combinatorial “guidance code” that defines how an axon (or dendrite) will find its way. An intriguing hypothesis is that synaptic partners might share similar guidance codes, ensuring that their processes meet at specific locations within the developing nervous system, as a first step in forming a neural circuit. In this issue of Neuron, Wu et al. (2011) provide compelling evidence to support this hypothesis. CH5424802 clinical trial They show that a combinatorial code involving Semaphorins

and their Plexin receptors guides the construction of a central neural circuit in the Drosophila embryo, involving MAPK inhibitor sensory neurons and their interneuronal partners. The developing Drosophila CNS expresses three Semaphorins, a transmembrane Sema-1a protein that signals through the Plexin A (PlexA) receptor, and the secreted Sema-2a and -2b proteins. While Sema-2a was known to act as a chemorepellant, signaling through the Plexin B receptor (PlexB; Ayoob et al., 2006), much less was known about either Sema-2b or its receptor. Sensory innervation of the embryonic CNS is perhaps less well known than other model systems in Drosophila, such as the eye, CNS midline, olfactory neuropil, or neuromuscular junction. Nevertheless, this paper shows it to be enormously powerful. The authors examined a group

of mechanosensory neurons called chordotonal (ch) cells, that are born in the periphery and whose axons grow along peripheral nerves to innervate the CNS. Once there, the axons are faced with the daunting challenge of identifying the correct tracts to lead them to their synaptic partners. In the CNS, they find that the roadways are still under construction, with axon tracts and fascicles actively being established. Wu et al. (2011) show that the ch neurons and their interneuron partners use the same molecular guidance system to rendezvous at a specific site within the developing ventral nerve cord (VNC, akin to the vertebrate spinal cord). The embryonic and larval VNC is organized as a latticework of longitudinal axon tracts that link the local segment-specific circuits together, and transverse of tracts that enable communication between the left and right hemisegments. A subset of the longitudinal axon tracts can be selectively labeled by virtue of their expression of the NCAM homolog Fasciclin2 (Fas2). This IgCAM is expressed by the axons of three parallel longitudinal tracts, known as the medial, intermediate, and lateral bundles, located on either side of the midline. Work by the Goodman lab (UC Berkeley) and the Dickson lab (Vienna, Austria) had shown that the spacing of these bundles is due to various degrees of chemorepulsion by Slit, a protein secreted by glial cells at the midline.