Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin

Dev Cell. 2004 Aug;7(2):205-16. doi: 10.1016/j.devcel.2004.07.007.

Abstract

Drosophila Flamingo is a 7-pass transmembrane cadherin that is necessary for dendritic patterning and axon guidance. How it works at the molecular level and whether homologs of Flamingo play similar roles in mammalian neurons or not have been unanswered questions. Here, we performed loss-of-function analysis using an RNAi system and organotypic brain slice cultures to address the role of a mammalian Flamingo homolog, Celsr2. Knocking down Celsr2 resulted in prominent simplification of dendritic arbors of cortical pyramidal neurons and Purkinje neurons, and this phenotype seemed to be due to branch retraction. Cadherin domain-mediated homophilic interaction appears to be required for the maintenance of dendritic branches. Furthermore, expression of various Celsr2 forms elicited distinct responses that were dependent on an extracellular subregion outside the cadherin domains and on a portion within the carboxyl intracellular tail. Based on these findings, we discuss how Celsr2 may regulate dendritic maintenance and growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Brain / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cadherins / physiology*
  • Cell Division
  • Cell Membrane / metabolism*
  • Dendrites / metabolism
  • Dendrites / physiology*
  • Dose-Response Relationship, Drug
  • Gene Deletion
  • Gene Silencing
  • Immunoblotting
  • Molecular Sequence Data
  • Neurons / metabolism
  • Phenotype
  • Plasmids / metabolism
  • Protein Structure, Tertiary
  • Purkinje Cells / metabolism
  • Pyramidal Cells / metabolism
  • RNA / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transfection

Substances

  • CELSR2 protein, human
  • Cadherins
  • RNA, Small Interfering
  • RNA