Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation

Belén Ramos, Brice Gaudillière, Azad Bonni, Grace Gill

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Integration of inputs by a neuron depends on dendritic arborization patterns. In mammals, the genetic programs that regulate dynamic remodeling of dendrites during development and in response to activity are incompletely understood. Here we report that knockdown of the transcription factor Sp4 led to an increased number of highly branched dendrites during maturation of cerebellar granule neurons in dissociated cultures and in cerebellar cortex. Time-course analysis revealed that depletion of Sp4 led to persistent generation of dendritic branches and a failure in resorption of transient dendrites. Depolarization induced a reduction in the number of dendrites, and knockdown of Sp4 blocked depolarization-induced remodeling. Furthermore, overexpression of Sp4 wild type, but not a mutant lacking the DNA-binding domain, was sufficient to promote dendritic pruning in nondepolarizing conditions. These findings indicate that the transcription factor Sp4 controls dendritic patterning during cerebellar development by limiting branch formation and promoting activity-dependent pruning.

Original languageEnglish
Pages (from-to)9882-9887
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number23
DOIs
StatePublished - Jun 5 2007

Keywords

  • Branching
  • Dendrite
  • Depolarization
  • Neuron
  • Pruning

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