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Transient Axonal Glycoprotein-1 (TAG-1) and Laminin-α1 Regulate Dynamic Growth Cone Behaviors and Initial Axon Direction in vivo
Neural Development
  • Marc A. Wolman, University of Wisconsin - Madison
  • Vinoth K. Sittaramane, University of Missouri
  • Jeffrey J. Essner, Iowa State University
  • H. Joseph Yost, University of Utah School of Medicine
  • Anand Chandrasekhar, University of Missouri
  • Mary C. Halloran, University of Wisconsin - Madison
Document Type
Article
Publication Version
Published Version
Publication Date
2-1-2008
DOI
10.1186/1749-8104-3-6
Abstract

Background. How axon guidance signals regulate growth cone behavior and guidance decisions in the complex in vivo environment of the central nervous system is not well understood. We have taken advantage of the unique features of the zebrafish embryo to visualize dynamic growth cone behaviors and analyze guidance mechanisms of axons emerging from a central brain nucleus in vivo. Results. We investigated axons of the nucleus of the medial longitudinal fascicle (nucMLF), which are the first axons to extend in the zebrafish midbrain. Using in vivo time-lapse imaging, we show that both positive axon-axon interactions and guidance by surrounding tissue control initial nucMLF axon guidance. We further show that two guidance molecules, transient axonal glycoprotein-1 (TAG-1) and laminin-α1, are essential for the initial directional extension of nucMLF axons and their subsequent convergence into a tight fascicle. Fixed tissue analysis shows that TAG-1 knockdown causes errors in nucMLF axon pathfinding similar to those seen in a laminin-α1 mutant. However, in vivo time-lapse imaging reveals that while some defects in dynamic growth cone behavior are similar, there are also defects unique to the loss of each gene. Loss of either TAG-1 or laminin-α1 causes nucMLF axons to extend into surrounding tissue in incorrect directions and reduces axonal growth rate, resulting in stunted nucMLF axons that fail to extend beyond the hindbrain. However, defects in axon-axon interactions were found only after TAG-1 knockdown, while defects in initial nucMLF axon polarity and excessive branching of nucMLF axons occurred only in laminin-α1 mutants. Conclusion. These results demonstrate how two guidance cues, TAG-1 and laminin-α1, influence the behavior of growth cones during axon pathfinding in vivo. Our data suggest that TAG-1 functions to allow growth cones to sense environmental cues and mediates positive axon-axon interactions. Laminin-α1 does not regulate axon-axon interactions, but does influence neuronal polarity and directional guidance.

Comments

This article is from Neural Development 3 (2008): 6, doi:10.1186/1749-8104-3-6. Posted with permission.

Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright Owner
Marc A. Wolman, et al
Language
en
File Format
application/pdf
Citation Information
Marc A. Wolman, Vinoth K. Sittaramane, Jeffrey J. Essner, H. Joseph Yost, et al.. "Transient Axonal Glycoprotein-1 (TAG-1) and Laminin-α1 Regulate Dynamic Growth Cone Behaviors and Initial Axon Direction in vivo" Neural Development Vol. 3 (2008) p. 1 - 14
Available at: http://works.bepress.com/jeffrey_essner/5/