Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice

Science. 2008 May 16;320(5878):946-9. doi: 10.1126/science.1155244.


Development of axonal tracts requires interactions between growth cones and the environment. Tracts such as the anterior commissure and internal capsule are defective in mice with null mutation of Celsr3. We generated a conditional Celsr3 allele, allowing regional inactivation. Inactivation in telencephalon, ventral forebrain, or cortex demonstrated essential roles for Celsr3 in neurons that project axons to the anterior commissure and subcerebral targets, as well as in cells that guide axons through the internal capsule. When Celsr3 was inactivated in cortex, subcerebral projections failed to grow, yet corticothalamic axons developed normally, indicating that besides guidepost cells, additional Celsr3-independent cues can assist their progression. These observations provide in vivo evidence that Celsr3-mediated interactions between axons and guidepost cells govern axonal tract formation in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Cadherins / genetics*
  • Cadherins / physiology*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Female
  • Gene Silencing
  • Internal Capsule / cytology
  • Internal Capsule / embryology
  • Internal Capsule / physiology
  • Male
  • Mice
  • Neural Pathways / embryology*
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Prosencephalon / cytology
  • Prosencephalon / embryology*
  • Prosencephalon / physiology
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / physiology*
  • Septal Nuclei / embryology
  • Septal Nuclei / physiology
  • Thalamus / cytology
  • Thalamus / embryology
  • Tissue Culture Techniques


  • Cadherins
  • Celsr3 protein, mouse
  • Receptors, Cell Surface