Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation.
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.
Ramos
Belén
B
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Gaudillière
Brice
B
Bonni
Azad
A
Gill
Grace
G
D000818:Animals; D019470:Biolistics; D002531:Cerebellum / Q000254:growth & development*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008156:Luciferases; D009474:Neurons / Q000166:cytology*; D009841:Oligonucleotides; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D051381:Rats; D051706:Sp4 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D009841:Oligonucleotides; D051706:Sp4 Transcription Factor; D008156:Luciferases