Growth cone stop signals: inviting to stay or sending away?

摘要

Axons growing into a target region must select appropriate cells on which to form synapses. A signal from a target cell may invite the appropriate axon to stop extension and initiate synapse formation, whereas a nontarget cell may act as an intermediate guidepost or signal an axon to avoid approaching and move on. The cerebellar cortex provides an ideal system in which to examine such interactions because a small number of cell types make specific, stereotyped connections. Baird et al. (1992) found that cultured cerebellar granule cells specifically arrested the growth of their afferents, the pontine mossy fibers. This result was interpreted to indicate that cerebellar granule cells signal to their afferents to stop growing and form a synapse. However, in their recent Journal of Neuroscience paper, Manzini et al. (2006) demonstrate that the cultured cerebellar granule cells more closely represent immature granule cells of the external germinal layer (EGL) and that absence of these immature granule cells in vivo leads to mossy fiber axon overgrowth. Thus, the arrest signal may instead prevent axons from entering a nontarget region containing immature cells.