Doublecortin-like Kinase Functions With Doublecortin to Mediate Fiber Tract Decussation and Neuronal Migration

Neuron. 2006 Jan 5;49(1):55-66. doi: 10.1016/j.neuron.2005.10.040.

Abstract

The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agenesis of Corpus Callosum
  • Aging / metabolism
  • Aging / physiology
  • Animals
  • Animals, Newborn / growth & development
  • Axons / metabolism
  • Brain / abnormalities
  • Brain / embryology*
  • Brain / growth & development*
  • Brain / metabolism
  • Cell Movement / physiology*
  • Cerebral Cortex / embryology
  • Congenital Abnormalities / genetics
  • Embryo, Mammalian / pathology
  • Embryonic Development
  • Exons / physiology
  • Gene Dosage
  • Gene Targeting
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology*
  • Nerve Fibers / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Synaptic Transmission / physiology

Substances

  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein
  • Dcamkl1 protein, mouse
  • Protein-Serine-Threonine Kinases