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Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration

Hiroyuki Koizumi1, Teruyuki Tanaka, Joseph G Gleeson

  • 1Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, La Jolla, California 93093, USA.

Neuron
|January 3, 2006
PubMed

Insights

The doublecortin-like kinase (Dclk) gene works with doublecortin (Dcx) in brain development. Together, they are crucial for neuronal migration and forming correct axonal connections in the brain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • The role of doublecortin (Dcx), a microtubule-associated protein, in brain development is debated.
  • Human mutations in Dcx cause severe cortical lamination defects, but mouse models show varied results.

Purpose of the Study:

  • To investigate the function of doublecortin-like kinase (Dclk) in neuronal development.
  • To clarify the relationship between Dcx and Dclk in cortical neuron migration and axonal wiring.

Main Methods:

  • Utilized RNAi-mediated knockdown and genetic analysis in mouse models.
  • Examined neuronal migration and axonal projection formation across the midline.
  • Assessed dosage-dependent genetic effects on neural connectivity.

Main Results:

  • Dclk functions in a partially redundant pathway with Dcx.
  • Both genes are essential for interhemispheric connectivity and neuronal migration.
  • RNAi knockdown of either Dcx or Dclk resulted in comparable neuronal migration defects.

Conclusions:

  • The doublecortin (Dcx) family of microtubule-associated proteins is vital for neuronal migration.
  • Proper axonal wiring and neuronal positioning depend on Dcx family function.

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