Visel Axel, Alvarez-Bolado Gonzalo, Thaller Christina, Eichele Gregor
Max Planck Institute of Experimental Endocrinology, Hannover, Germany.
J Comp Neurol. 2006 Jun 10;496(5):684-97. doi: 10.1002/cne.20953.
Adenylate cyclases (Adcys) are components of several developmentally, neurophysiologically, and pharmacologically relevant signaling pathways. A prominent feature of Adcys is their ability to integrate multiple signaling pathways into a single second messenger pathway, the production of cAMP. Nine isoforms of membrane-bound Adcys are known, each encoded by a distinct gene. These isoforms differ in their response to regulatory upstream pathways as well as in their distribution in the brain and elsewhere. Use of various detection methods and animal species has, however, hampered a direct comparison of expression patterns, so the potential contribution of single isoforms to Adcy activity in different brain regions remains unclear. We have determined the expression patterns of all nine Adcy genes in the embryonic, postnatal day 7, and adult mouse brain by nonradioactive robotic in situ hybridization (ISH). Here we describe the salient features of these patterns. Regional colocalization of Adcy transcripts encoding isoforms with different regulatory properties was detected in the cortex, subregions of the hippocampus, olfactory bulb, thalamus, and striatum. Hence, our expression data support models for modulation of cAMP signaling by combinatorial action of multiple Adcy isoforms. However, in several instances, the expression domains of genes encoding isoforms with similar regulatory properties spatially exclude each other, which is most evident in not previously described expression domains of the embryonic midbrain roof. This is suggestive of functional specialization.
腺苷酸环化酶（Adcys）是多种与发育、神经生理学和药理学相关的信号通路的组成部分。Adcys的一个显著特征是它们能够将多种信号通路整合到单一的第二信使通路中，即cAMP的产生。已知有九种膜结合型Adcys同工型，每种由一个不同的基因编码。这些同工型在对上游调节通路的反应以及在大脑和其他部位的分布方面存在差异。然而，使用各种检测方法和动物物种阻碍了对表达模式的直接比较，因此单个同工型对不同脑区Adcy活性的潜在贡献仍不清楚。我们通过非放射性机器人原位杂交（ISH）确定了所有九个Adcy基因在胚胎期、出生后第7天和成年小鼠大脑中的表达模式。在此我们描述这些模式的显著特征。在皮质、海马体亚区域、嗅球、丘脑和纹状体中检测到编码具有不同调节特性的同工型的Adcy转录本的区域共定位。因此，我们的表达数据支持了多个Adcy同工型通过组合作用调节cAMP信号的模型。然而，在一些情况下，编码具有相似调节特性的同工型的基因的表达域在空间上相互排斥，这在胚胎中脑顶盖以前未描述的表达域中最为明显。这暗示了功能特化。
