Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex.
Dendrite branching and spine formation determines the function of morphologically distinct and specialized neuronal subclasses. However, little is known about the programs instructing specific branching patterns in vertebrate neurons and whether such programs influence dendritic spines and synapses. Using knockout and knockdown studies combined with morphological, molecular, and electrophysiological analysis, we show that the homeobox Cux1 and Cux2 are intrinsic and complementary regulators of dendrite branching, spine development, and synapse formation in layer II-III neurons of the cerebral cortex. Cux genes control the number and maturation of dendritic spines partly through direct regulation of the expression of Xlr3b and Xlr4b, chromatin remodeling genes previously implicated in cognitive defects. Accordingly, abnormal dendrites and synapses in Cux2(-/-) mice correlate with reduced synaptic function and defects in working memory. These demonstrate critical roles of Cux in dendritogenesis and highlight subclass-specific mechanisms of synapse regulation that contribute to the establishment of cognitive circuits.
Cubelos
Beatriz
B
Centro Nacional de Biotecnología, CSIC, Darwin 3, Campus de Cantoblanco, Madrid 28049, Spain.
Sebastián-Serrano
Alvaro
A
Beccari
Leonardo
L
Calcagnotto
Maria Elisa
ME
Cisneros
Elsa
E
Kim
Seonhee
S
Dopazo
Ana
A
Alvarez-Dolado
Manuel
M
Redondo
Juan Miguel
JM
Bovolenta
Paola
P
Walsh
Christopher A
CA
Nieto
Marta
M
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014157:Transcription Factors
C080632:CUX1 protein, human; C101672:Cux2 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors