Species differences in the expression of Ahi1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies.
Species differences in the expression of Ahi1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies.
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DOI：
10.1002/cne.21824
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发表时间：
2008-11-10
影响因子：
2.5
通讯作者：
Ferland, Russell J.
中科院分区：
文献类型：
--
作者：
Doering, Jennifer E.;Kane, Kelly;Hsiao, Yi-Chun;Yao, Cong;Shi, Bingxing;Slowik, Amber D.;Dhagat, Bakul;Scott, Delisha D.;Ault, Jeffrey G.;Page-McCaw, Patrick S.;Ferland, Russell J.
Joubert 综合征 (JBTS) 是一种常染色体隐性遗传疾病，其特征是小脑和脑干畸形。 JBTS 患者呼吸和眼球运动异常、共济失调、肌张力减退和认知困难，并表现出镜像运动。 Abelson-helper 整合位点 1 基因 (AHI1) 的突变会导致人类 JBTS，这表明 AHI1 是后脑发育所必需的；然而，AHI1 也可能是神经元功能所必需的。研究表明 AHI1 基因座与精神分裂症有关，这一观点得到了支持。为了进一步了解 AHI1 在发育和成熟中枢神经系统中的功能，我们确定了 AHI1 直系同源基因产物在人类、小鼠和斑马鱼整个发育过程中的空间和时间表达模式。小鼠 Ahi1 分布在神经元的细胞质、树突和轴突中，但在神经胶质细胞中不存在。早在胚胎第 10.5 天就观察到小鼠大脑中的 Ahi1 表达，并持续到成年期，在出生后第一周达到峰值表达。在小鼠后脑、中脑和腹侧前脑的神经元中观察到 Ahi1。一般来说，AHI1/Ahi1/ahi1直向同源物在人类、小鼠和斑马鱼中具有保守的分布模式，但小鼠Ahi1在发育和成熟的小脑中不存在。 Ahi1 在柱状体中也得到了一致的观察，柱状体是神经元中发现的一种特征较差的细胞质细胞器。总体而言，这些结果表明 AHI1 在神经发育过程中的作用，而神经发育过程是 JBTS 中大多数神经解剖学缺陷的基础，并且可能在导致精神分裂症的神经元功能中发挥作用。
Joubert syndrome (JBTS) is an autosomal recessive disorder characterized by cerebellum and brainstem malformations. Individuals with JBTS have abnormal breathing and eye movements, ataxia, hypotonia, and cognitive difficulty, and they display mirror movements. Mutations in the Abelson-helper integration site-1 gene (AHI1) cause JBTS in humans, suggesting that AHI1 is required for hindbrain development; however AHI1 may also be required for neuronal function. Support for this idea comes from studies demonstrating that the AHI1 locus is associated with schizophrenia. To gain further insight into the function of AHI1 in both the developing and mature CNS, we determined the spatial and temporal expression patterns of the gene products of AHI1 orthologs throughout development, in human, mouse, and zebrafish. Murine Ahi1 was distributed throughout the cytoplasm, dendrites, and axons of neurons, but was absent in glial cells. Ahi1 expression in the mouse brain was observed as early as embryonic day 10.5 and persisted into adulthood, with peak expression during the first post-natal week. Murine Ahi1 was observed in neurons of the hindbrain, midbrain, and ventral forebrain. Generally, the AHI1/Ahi1/ahi1 orthologs had a conserved distribution pattern in human, mouse, and zebrafish, but mouse Ahi1 was not present in the developing and mature cerebellum. Ahi1 was also observed consistently in the stigmoid body, a poorly characterized cytoplasmic organelle found in neurons. Overall, these results suggest roles for AHI1 in neurodevelopmental processes that underlie most of the neuroanatomical defects in JBTS, and perhaps in neuronal functions that contribute to schizophrenia.
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影响因子：
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作者：
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通讯作者：
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Stefansson, Hreinn
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作者：
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