Retinoid-related orphan receptor alpha controls the early steps of Purkinje cell dendritic differentiation

J Neurosci. 2006 Feb 1;26(5):1531-8. doi: 10.1523/JNEUROSCI.4636-05.2006.

Abstract

Dendritic differentiation involves both regressive and growth events. The mechanisms controlling the regressive events are poorly understood. This study is aimed at determining the role of the nuclear receptor retinoid-related orphan receptor alpha (RORalpha) in Purkinje cell (PC) dendritic differentiation in organotypic cultures. As observed in vivo, in these cultures, fusiform PCs with embryonic bipolar shape undergo regression before the outgrowth of the ultimate dendritic tree. We show that lentiviral-mediated hRORalpha1 overexpression in fusiform PCs leads to a cell-autonomous accelerated progression of dendritic differentiation. In addition, RORalpha is necessary for the PC regressive events: whereas staggerer RORalpha-deficient PCs remain in the embryonic fusiform stage, replacement of hRORalpha1 restores normal dendritogenesis. These results demonstrate that RORalpha expression in fusiform PCs is crucial for the dendritic regression and progression of the following step of extension of dendritic processes. However, it does not seem to participate to the last stage of dendritic growth. This study identifies RORalpha as a nuclear receptor crucial for the control of dendritic remodeling during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Dendrites / ultrastructure*
  • Genetic Vectors
  • Kinetics
  • Lentivirus / genetics
  • Mice
  • Mice, Neurologic Mutants
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • Organ Culture Techniques
  • Purkinje Cells / cytology*
  • Purkinje Cells / metabolism
  • Receptor Protein-Tyrosine Kinases
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cytoplasmic and Nuclear / deficiency
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*

Substances

  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • RORA protein, human
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • ROR1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor Tyrosine Kinase-like Orphan Receptors