|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online November 21, 2006
doi: 10.1242/10.1242/dev.02711
1 Department of Genetics, Cell Biology and Development and the Developmental
Biology Center, University of Minnesota, Minneapolis, MN 55455, USA.
2 Howard Hughes Medical Institute, Minneapolis, MN 55455, USA.
* Author for correspondence (e-mail: moconnor{at}umn.edu)
Accepted 23 October 2006
Proper axon pathfinding requires that growth cones execute appropriate turns and branching at particular choice points en route to their synaptic targets. Here we demonstrate that the Drosophila metalloprotease tolloid-related (tlr) is required for proper fasciculation/defasciculation of motor axons in the CNS and for normal guidance of many motor axons enroute to their muscle targets. Tlr belongs to a family of developmentally important proteases that process various extracellular matrix components, as well as several TGF-ß inhibitory proteins and pro-peptides. We show that Tlr is a circulating enzyme that processes the pro-domains of three Drosophila TGF-ß-type ligands, and, in the case of the Activin-like protein Dawdle (Daw), this processing enhances the signaling activity of the ligand in vitro and in vivo. Null mutants of daw, as well as mutations in its receptor babo and its downstream mediator Smad2, all exhibit axon guidance defects that are similar to but less severe than tlr. We suggest that by activating Daw and perhaps other TGF-ß ligands, Tlr provides a permissive signal for axon guidance.
Key words: BMP, Activin, Fasciculation, Drosophila
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  M. Siebert, D. Banovic, B. Goellner, and H. Aberle Drosophila motor axons recognize and follow a Sidestep-labeled substrate pathway to reach their target fields Genes & Dev., May 1, 2009; 23(9): 1052 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ng TGF{beta} signals regulate axonal development through distinct Smad-independent mechanisms Development, December 15, 2008; 135(24): 4025 - 4035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Batut, B. Schmierer, J. Cao, L. A. Raftery, C. S. Hill, and M. Howell Two highly related regulatory subunits of PP2A exert opposite effects on TGF-{beta}/Activin/Nodal signalling Development, September 1, 2008; 135(17): 2927 - 2937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. Williamson and P. R. Hiesinger Synaptic Patterning by Morphogen Signaling Sci. Signal., May 6, 2008; 1(18): pe20 - pe20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Zhu, J. Q. Boone, P. A. Jensen, S. Hanna, L. Podemski, J. Locke, C. Q. Doe, and M. B. O'Connor Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain Development, February 1, 2008; 135(3): 513 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Miller, A. Page-McCaw, and H. T. Broihier Matrix metalloproteinases promote motor axon fasciculation in the Drosophila embryo Development, January 1, 2008; 135(1): 95 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, C. L. Hehr, K. Atkinson-Leadbeater, J. C. Hocking, and S. McFarlane Targeting of Retinal Axons Requires the Metalloproteinase ADAM10 J. Neurosci., August 1, 2007; 27(31): 8448 - 8456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Parker, J. E. Ellis, M. Q. Nguyen, and K. Arora The divergent TGF-{beta} ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila. Development, December 1, 2006; 133(24): 4981 - 4991. [Abstract] [Full Text] [PDF]
|
|
