Function of neurolin (DM-GRASP/SC-1) in guidance of motor axons during zebrafish development

Neurolin (zf DM-GRASP), a transmembrane protein with five extracellular imm unoglobulin domains, is expressed by secondary but not primary motoneurons during zebrafish development. The spatiotemporally restricted expression pa ttern suggests that Neurolin plays a role in motor axon growth and guidance . To test this hypothesis, we injected zebrafish embryos with function-bloc king Neurolin antibodies. In injected embryos, secondary motor axons form a broadened bundle along the common path and ectopic branches leave the comm on path at right angles. Moreover, the formation of the ventral and the ros tral projection of secondary motor axons is inhibited during the second day of development. Pathfinding errors, resulting in secondary motor axons gro wing through ectopic regions of the somites, occur along the common path an d in the dorsal and rostral projection. Our data are compatible with the vi ew that Neurolin is involved in the recognition of guidance cues and acts a s a receptor on secondary motor axons. Consistent with this idea is the bin ding pattern of a soluble Neurolin-Fc construct showing that putative ligan ds are distributed along the common path, the ventral projection, and in th e area where the rostral projection develops. (C) 2001 Academic Press.