title: CTCF is required for neural development and stochastic expression of clustered Pcdh genes in neurons.
abstract: The CCCTC-binding factor (CTCF) is a key molecule for chromatin conformational changes that promote cellular diversity, but nothing is known about its role in neurons. Here, we produced mice with a conditional knockout (cKO) of CTCF in postmitotic projection neurons, mostly in the dorsal telencephalon. The CTCF-cKO mice exhibited postnatal growth retardation and abnormal behavior and had defects in functional somatosensory mapping in the brain. In terms of gene expression, 390 transcripts were expressed at significantly different levels between CTCF-deficient and control cortex and hippocampus. In particular, the levels of 53 isoforms of the clustered protocadherin (Pcdh) genes, which are stochastically expressed in each neuron, declined markedly. Each CTCF-deficient neuron showed defects in dendritic arborization and spine density during brain development. Their excitatory postsynaptic currents showed normal amplitude but occurred with low frequency. Our results indicate that CTCF regulates functional neural development and neuronal diversity by controlling clustered Pcdh expression.
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Hirayama
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tarusawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D000076246:CCCTC-Binding Factor; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; D015820:Cadherins; C000619698:Ctcf protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins