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First published online November 21, 2006

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Axons dawdle to the target

During nervous system development, axons are guided to their targets by attractive and repulsive cues that control the direction of axon growth, and by molecules that have general permissive or inhibitory effects on growth cone behaviour. Several specific guidance cues are well characterised but two papers in this issue provide the first evidence that activin signalling plays a permissive role in motoneuron axon guidance in Drosophila. On p. 4981, Parker and colleagues report that the divergent transforming growth factor ß (Tgfß) ligand Dawdle (Daw), which is expressed in glia and mesoderm, acts through an activin signalling pathway to influence motoneuron path finding. They show that intersegmental and segmental motoneurons do not extend completely or innervate their targets in daw mutants. They then provide biochemical evidence that Daw initiates an activin signalling pathway via the type-1 Tgfß receptor Baboon (Babo), the type-II receptor Punt, and the signal-transducer Smad2. Mutations in these signalling components, they report, cause similar defects in axonal pathfinding to daw mutations; other experiments indicate that Daw plays a permissive role in axon guidance by possibly modulating growth cone responses to other guidance cues. On p. 4969, Serpe and O'Connor report that the metalloproteinase Tolloid-related (Tlr) also provides a permissive signal for motoneuron axon guidance in Drosophila by activating Daw and possibly other Tgfß ligands. Increasing evidence suggests that metalloproteinases modulate the activity of guidance cues during neural development, in part by processing the components of guidance pathways. Here Serpe and O'Connor show that Tlr is required for the proper bundling/unbundling, and for the normal guidance, of many motoneuron axons in the CNS. Tlr, they report, processes the pro-domains of three Drosophila Tgfß ligands; in the case of Daw, this processing enhances its signalling activity in vitro and in vivo. Finally, they show that daw-null mutants, babo mutants and Smad2 mutants develop guidance defects that are similar to, but less severe than, those caused by tlr mutations. Taken together, therefore, these two papers provide strong evidence for a novel role for activin signalling in axon guidance.

Related articles in Development:

The metalloprotease Tolloid-related and its TGF-ß-like substrate Dawdle regulate Drosophila motoneuron axon guidance

Mihaela Serpe and Michael B. O'Connor
Development 2006 133: 4969-4979. [Abstract] [Full Text]  

The divergent TGF-ß ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila

Louise Parker, Jeremy E. Ellis, Minh Q. Nguyen, and Kavita Arora
Development 2006 133: 4981-4991. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content