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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
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N-cadherin specifies first asymmetry in developing neurons.

Annette Gärtner1, Eugenio F Fornasiero, Sebastian Munck

  • 1VIB Center for the Biology of Disease, KULeuven Center for Human Genetics, Leuven, Belgium. Annette.Gaertner@cme.vib-kuleuven.be

The EMBO Journal
|February 23, 2012
PubMed
Summary

N-cadherin concentration at one pole of newborn neurons initiates neurite outgrowth, guiding brain wiring. This early N-cadherin polarization is crucial for establishing neuronal polarity and correct brain development.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Precise neuronal polarization and orientation are critical for proper brain wiring.
  • Pyramidal neurons establish polarity via neurite sprouting, influencing migration and domain formation.

Purpose of the Study:

  • To investigate the role of N-cadherin in the initial polarization of developing neurons.
  • To determine the molecular mechanisms regulating the establishment of neuronal polarity.

Main Methods:

  • Immunofluorescence microscopy to track N-cadherin localization.
  • Experiments with ectopic N-cadherin expression.
  • In vivo loss-of-function studies using non-functional N-cadherin.
  • Analysis of Golgi and centrosome movement.

Main Results:

  • Endogenous N-cadherin accumulates at one pole of newborn neurons, preceding neurite emergence.
  • Ectopic N-cadherin expression directs the site of the first neurite.
  • Golgi and centrosome repositioning is regulated by PI3K and cytoskeleton dynamics.
  • Loss of N-cadherin function leads to misorientation of the neuronal cell axis in vivo.

Conclusions:

  • N-cadherin polarization is an early and essential event in establishing neuronal polarity.
  • N-cadherin acts as a key determinant for the site of initial neurite outgrowth.
  • This mechanism is fundamental for the correct wiring and development of the brain.