KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Cell Rep. 2012 Aug 30;2(2):345-57. doi: 10.1016/j.celrep.2012.06.014. Epub 2012 Jul 26.
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.
CCCTC 结合因子（CTCF）是促进细胞多样性的染色质构象变化的关键分子，但尚不清楚其在神经元中的作用。在这里，我们通过条件性敲除（cKO）出生后有丝分裂后投射神经元（主要在背侧端脑）中的 CTCF 产生了小鼠。CTCF-cKO 小鼠表现出出生后生长迟缓和异常行为，并在大脑中的感觉功能映射中存在缺陷。在基因表达方面，CTCF 缺失的皮质和海马体与对照组之间有 390 个转录本的表达水平存在显著差异。特别是，簇状原钙黏蛋白（Pcdh）基因的 53 种异构体的表达水平明显下降，这些基因在每个神经元中随机表达。在大脑发育过程中，每个 CTCF 缺失的神经元的树突分支和棘密度都存在缺陷。它们的兴奋性突触后电流幅度正常，但频率较低。我们的结果表明，CTCF 通过控制簇状 Pcdh 表达来调节功能性神经发育和神经元多样性。
