Ishii Yoko, Kawaguchi Makoto, Takagawa Kiyoshi, Oya Takeshi, Nogami Shigeharu, Tamura Amane, Miura Yutaka, Ido Akio, Sakata Nobuo, Hashimoto-Tamaoki Tomoko, Kimura Tomoatsu, Saito Takayoshi, Tamaoki Taiki, Sasahara Masakiyo
Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
J Comp Neurol. 2003 Oct 6;465(1):57-71. doi: 10.1002/cne.10807.
The ATBF1 gene encodes transcription factors containing four homeodomains and multiple zinc finger motifs. However, the gene products have yet to be identified and the role remains unknown in vivo. In this study, we raised an antiserum for ATBF1 and found high levels of expression of ATBF1 in developing rat brain. Western and Northern blot analyses detected a 400 kDa protein and 12.5 kb mRNA in developing rat brain, respectively; both corresponding to ATBF1-A but not the B isoform. The protein was highly expressed in the midbrain and diencephalon and mRNA was highly expressed in the brainstem, mostly in embryo and neonatal brain. Immunohistochemistry identified postmitotic neurons in the brainstem as the major site of ATBF1 expression, and the expression levels varied depending on age of and location in the brain. Expression was transient and weak in the precursor cells at early neurogenesis. ATBF1 decreased postnatally, but remained in mature neurons, including those expressing DOPA decarboxylase (DDC). High levels of ATBF1 were expressed in precursor cells in accordance with neurogenesis and were continued to the mature neurons in specific areas such as the inferior colliculus. Expression was not significant from precursor cells to mature neurons in the cerebral cortex and hippocampus. ATBF1 and its Drosophila homolog, Zfh-2, are known to regulate cell differentiation and proliferation via the interaction with either of the basic helix-loop-helix transcription factors, c-myb, or the DDC gene. Together with these reported functions the expression features detected here suggest that ATBF1 may participate in the regulation of neuronal cell maturation or region-specific central nervous system differentiation.
ATBF1基因编码含有四个同源结构域和多个锌指基序的转录因子。然而，该基因产物尚未被鉴定，其在体内的作用仍然未知。在本研究中，我们制备了针对ATBF1的抗血清，并发现ATBF1在发育中的大鼠脑中高表达。蛋白质免疫印迹和Northern印迹分析分别在发育中的大鼠脑中检测到一种400 kDa的蛋白质和12.5 kb的mRNA；两者均对应于ATBF1-A而非B异构体。该蛋白质在中脑和间脑中高表达，mRNA在脑干中高表达，主要在胚胎和新生脑中。免疫组织化学鉴定脑干中的有丝分裂后神经元是ATBF1表达的主要部位，其表达水平因脑的年龄和位置而异。在神经发生早期，前体细胞中的表达短暂且微弱。ATBF1在出生后减少，但保留在成熟神经元中，包括那些表达多巴脱羧酶（DDC）的神经元。随着神经发生，前体细胞中表达高水平的ATBF1，并在特定区域如中脑下丘持续到成熟神经元。在大脑皮层和海马体中，从前体细胞到成熟神经元的表达不明显。已知ATBF1及其果蝇同源物Zfh-2通过与基本螺旋-环-螺旋转录因子c-myb或DDC基因相互作用来调节细胞分化和增殖。结合这些已报道的功能，此处检测到的表达特征表明ATBF1可能参与神经元细胞成熟或区域特异性中枢神经系统分化的调节。
