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p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory pathway

W R Morse1, J G Whitesides, A S LaMantia

  • 1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA.

Journal of Neurobiology
|July 11, 1998
PubMed
Summary
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Src-family tyrosine kinases, including p59fyn and pp60c-src, are crucial for olfactory nerve axon fasciculation. Genetic mutations in these kinases disrupt axon guidance, highlighting their essential roles in neural development.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Src-family tyrosine kinases, specifically p59fyn and pp60c-src, are present in olfactory nerve axons during early growth.
  • The precise functional roles of these kinases in axonal development are not fully understood.

Purpose of the Study:

  • To investigate the function of p59fyn and pp60c-src in olfactory nerve axon trajectory and fasciculation.
  • To analyze the effects of single and double gene knockouts of src and fyn on olfactory nerve development.

Main Methods:

  • Analysis of olfactory nerve trajectory in E11.5 homozygous null mutant mice (single src/fyn mutants and double src/fyn mutants).
  • Assessment of axonal fasciculation using NCAM labeling.
  • Examination of vomeronasal axon coalescence and mesenchymal adhesive environment (laminin, fibronectin staining).

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Main Results:

  • Primary olfactory axons successfully projected to the telencephalon in all mutant groups.
  • Src/fyn double mutants exhibited the most significant defasciculation, while fyn-minus mutants had more fascicles than src-minus mutants.
  • Subtle changes in mesenchymal laminin and fibronectin suggest their contribution to fasciculation defects.

Conclusions:

  • Signaling pathways involving p59fyn and pp60c-src are essential for proper axon fasciculation in the developing olfactory system.
  • These kinases appear to have partially compensatory mechanisms for axonal adhesion and guidance.
  • Defects in fasciculation are not attributed to changes in olfactory epithelium size.