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发育中和成熟大脑中Foxp2和Foxp1 mRNA及蛋白的特征分析。

Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain.

作者信息

Ferland Russell J, Cherry Timothy J, Preware Patricia O, Morrisey Edward E, Walsh Christopher A

机构信息

Department of Neurology, Beth Israel Deaconess Medical Center, Howard Hughes Medical Institute, Harvard Medical School, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.

出版信息

J Comp Neurol. 2003 May 26;460(2):266-79. doi: 10.1002/cne.10654.

Abstract

Foxp2 and Foxp1 are recently identified members of the Fox family of winged-helix/forkhead transcription factor genes. A recent study has found that mutations in human FOXP2 produce a severe language disorder. Since Foxp2 appears to be important in language, we wanted to explore the expression of this gene and a homologous gene, Foxp1, in the developing brain. In the present study, we investigated the time course and localization of Foxp2 and Foxp1 mRNA and protein expression in the developing and adult mouse using in situ hybridization and immunohistochemistry. Foxp2 and Foxp1 are expressed as early as E12.5 and persist into adulthood. Foxp2 and Foxp1 were most highly expressed in the developing and mature basal ganglia. Expression of Foxp2 was also observed in the cerebral cortex (layer 6), cerebellum (Purkinje neurons), and thalamus. Foxp1 expression was observed in the cerebral cortex (layers 3-5), hippocampus (CA1), and thalamus. Very little ventricular zone expression was observed for Foxp2 and Foxp1 and the expression of both of these genes occurred following neuronal migration, suggesting a role for these genes in postmigratory neuronal differentiation. Furthermore, we demonstrated the expression of FOXP2 in human fetal brain by RT-PCR, in the perisylvian area of the left and right cerebral hemispheres, as well as in the frontal and occipital cortices. Overall, the widespread expression of Foxp2 in the developing brain makes it difficult to draw specific conclusions about which areas of Foxp2 expression are critical to human language function.

摘要

Foxp2和Foxp1是最近在有翼螺旋/叉头转录因子基因的Fox家族中被鉴定出的成员。最近的一项研究发现,人类FOXP2基因的突变会导致严重的语言障碍。由于Foxp2似乎在语言方面起着重要作用,我们想要探究该基因以及一个同源基因Foxp1在发育中的大脑中的表达情况。在本研究中,我们利用原位杂交和免疫组织化学技术,研究了Foxp2和Foxp1 mRNA及蛋白在发育中和成年小鼠大脑中的表达时间进程和定位。Foxp2和Foxp1早在胚胎第12.5天就开始表达,并持续至成年期。Foxp2和Foxp1在发育中和成熟的基底神经节中表达最高。在大脑皮层(第6层)、小脑(浦肯野神经元)和丘脑也观察到了Foxp2的表达。在大脑皮层(第3 - 5层)、海马体(CA1)和丘脑中观察到了Foxp1的表达。对于Foxp2和Foxp1,在脑室区观察到的表达非常少,并且这两个基因的表达都发生在神经元迁移之后,这表明这些基因在迁移后神经元分化中发挥作用。此外,我们通过RT-PCR证明了FOXP2在人类胎儿大脑中的表达,在左右大脑半球的颞周区以及额叶和枕叶皮质中均有表达。总体而言,Foxp2在发育中的大脑中广泛表达,这使得难以就Foxp2表达的哪些区域对人类语言功能至关重要得出具体结论。

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