Protocadherin Celsr3 is crucial in axonal tract development

Nat Neurosci. 2005 Apr;8(4):451-7. doi: 10.1038/nn1428. Epub 2005 Mar 20.


In the embryonic CNS, the development of axonal tracts is required for the formation of connections and is regulated by multiple genetic and microenvironmental factors. Here we show that mice with inactivation of Celsr3, an ortholog of Drosophila melanogaster flamingo (fmi; also known as starry night, stan) that encodes a seven-pass protocadherin, have marked, selective anomalies of several major axonal fascicles, implicating protocadherins in axonal development in the mammalian CNS for the first time. In flies, fmi controls planar cell polarity (PCP) in a frizzled-dependent but wingless-independent manner. The neural phenotype in Celsr3 mutant mice is similar to that caused by inactivation of Fzd3, a member of the frizzled family. Celsr3 and Fzd3 are expressed together during brain development and may act in synergy. Thus, a genetic pathway analogous to the one that controls PCP is key in the development of the axonal blueprint.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Body Patterning / physiology*
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Cadherins / physiology*
  • Carbocyanines / metabolism
  • Cloning, Molecular / methods
  • Diaphragm / metabolism
  • Frizzled Receptors
  • Gene Expression Regulation, Developmental / physiology*
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Mutagenesis / physiology
  • Mutation / physiology
  • Neurofilament Proteins / metabolism
  • Neurons / metabolism
  • Neurons / ultrastructure
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Silver Staining / methods


  • 3,3'-dihexadecylindocarbocyanine
  • Cadherins
  • Carbocyanines
  • Celsr3 protein, mouse
  • Frizzled Receptors
  • Fzd3 protein, mouse
  • Neurofilament Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled