Crossing a line in axon guidance

In bilaterally symmetric animals, the central nervous system is divided into two halves, and, during development, the proper formation of neuronal circuitry sometimes requires that axons choose whether they should project to the same side (ipsilateral) or to the opposite side (contralateral) of the embryonic midline. Many axon guidance molecules contribute to this decision,but little is known of their transcriptional regulation. Now in their study of the optic chiasm - the neuronal structure required for binocular vision -Eloísa Herrera and colleagues(p. 1833) report, for the first time, a link between a transcription factor (Zic2) and an axon guidance molecule (EphB1) in controlling axonal laterality. By manipulating Zic2 expression in EphB1-expressing and EphB1-null mice, they show that Zic2 is sufficient to switch the contralateral trajectory of retinal axons to an ipsilateral one. Zic2 can do this via both EphB1-dependent and -independent mechanisms. From their findings, the authors propose that transcription factors can directly and sequentially activate different guidance receptors throughout an axon's journey.