Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex

Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex
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DOI:
10.1038/980
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发表时间:
1998-07-01
期刊:
影响因子:
30.8
通讯作者:
Neumann, PE
Neumann, PE
中科院分区:
生物学1区
文献类型:
--
作者:
Abdel-Majid, RM;Leong, WL;Neumann, PE

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小鼠的躯体感觉(SI)皮层在第IV层显示出一种模式化的、不均匀的神经元分布,称为“桶场”(参考文献1)。终止于第IV层的丘脑皮质传入(TCAs)被隔离,使得每个桶,一个容易看到的圆柱形阵列的神经元周围的细胞稀疏的中心,代表一个独特的感受野。TCA乔木被限制在桶中空和突触上的桶壁神经元,其树突朝向桶的中心(2)。在洛桑大学(瑞士)的ICR原种中自发发生的无桶(brl)突变的纯合子小鼠,不能形成这种神经元的模式化分布,但仍然显示出SI皮层的正常拓扑组织(3)。尽管没有桶和重叠区的TCA树枝状,个别晶须表示的大小,判断2-脱氧葡萄糖摄取,是类似的野生型小鼠。我们确定腺苷酸环化酶I型(Adcy 1)的基因破坏在brl突变小鼠近端染色体11,酶测定,突变分析和检查小鼠纯合子的Adcy 1的有针对性的破坏的精细映射。这些结果提供了第一个证据cAMP信号通路参与模式形成的大脑。
The somatosensory (SI) cortex of mice displays a patterned, nonuniform distribution of neurons in layer IV called the "barrelfield' (ref. 1). Thalamocortical afferents (TCAs) that terminate in layer IV are segregated such that each barrel, a readily visible cylindrical array of neurons surrounding a cell-sparse center, represents a distinct receptive field. TCA arbors are confined to the barrel hollow and synapse on barrel-wail neurons whose dendrites are oriented toward the center of the barrel(2). Mice homozygous for the barrelless (brl) mutation, which occurred spontaneously in ICR stock at Universitd de Lausanne (Switzerland), fail to develop this patterned distribution of neurons, but still display normal topological organization of the SI cortex(3). Despite the absence of barrels and the overlapping zones of TCA arborization, the size of individual whisker representations, as judged by 2-deoxyglucose uptake, is similar to that of wild-type mice. We identified adenylyl cyclase type I(Adcy1) as the gene disrupted in brl mutant mice by fine mapping of proximal chromosome 11, enzyme assay, mutation analysis and examination of mice homozygous for a targeted disruption of Adcy1. These results provide the first evidence for involvement of cAMP signalling pathways in pattern formation of the brain.