PUBLICATION

Chondrolectin mediates growth cone interactions of motor axons with an intermediate target

Authors
Zhong, Z., Ohnmacht, J., Reimer, M.M., Bach, I., Becker, T., and Becker, C.G.
ID
ZDB-PUB-120330-1
Date
2012
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   32(13): 4426-4439 (Journal)
Registered Authors
Becker, Catherina G., Becker, Thomas, Ohnmacht, Jochen, Reimer, Michell M.
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Axons/physiology*
  • Female
  • Gene Expression Profiling/methods
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques/methods
  • Growth Cones/physiology*
  • LIM-Homeodomain Proteins/antagonists & inhibitors
  • LIM-Homeodomain Proteins/genetics
  • Lectins, C-Type/genetics
  • Lectins, C-Type/physiology*
  • Male
  • Motor Neurons/cytology
  • Motor Neurons/physiology*
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
22457492 Full text @ J. Neurosci.
Abstract

The C-type lectin chondrolectin (chodl) represents one of the major gene products dysregulated in spinal muscular atrophy models in mice. However, to date, no function has been determined for the gene. We have identified chodl and other novel genes potentially involved in motor axon differentiation, by expression profiling of transgenically labeled motor neurons in embryonic zebrafish. To enrich the profile for genes involved in differentiation of peripheral motor axons, we inhibited the function of LIM-HDs (LIM homeodomain factors) by overexpression of a dominant-negative cofactor, thereby rendering labeled axons unable to grow out of the spinal cord. Importantly, labeled cells still exhibited axon growth and most cells retained markers of motor neuron identity. Functional tests of chodl, by overexpression and knockdown, confirm crucial functions of this gene for motor axon growth in vivo. Indeed, knockdown of chodl induces arrest or stalling of motor axon growth at the horizontal myoseptum, an intermediate target and navigational choice point, and reduced muscle innervation at later developmental stages. This phenotype is rescued by chodl overexpression, suggesting that correct expression levels of chodl are important for interactions of growth cones of motor axons with the horizontal myoseptum. Combined, these results identify upstream regulators and downstream functions of chodl during motor axon growth.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes