ONTOGENY AND DISTRIBUTION OF GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) MESSENGER-RNA IN RAT
ONTOGENY AND DISTRIBUTION OF GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) MESSENGER-RNA IN RAT
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DOI：
10.1016/0165-3806(94)00197-8
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发表时间：
1995-03-16
期刊：
影响因子：
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通讯作者：
BOHN, MC
中科院分区：
文献类型：
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作者：
CHOILUNDBERG, DL;BOHN, MC
神经胶质细胞系来源的神经营养因子（GDNF）是从大鼠神经胶质肿瘤细胞系B49中分离出来的转化生长因子- β家族的成员。在体外培养的胚胎多巴胺能（DA）神经元中，GDNF促进存活、高亲和多巴胺摄取和神经突生长。采用GDNF特异性引物的半定量逆转录聚合酶链反应（RT-PCR）技术，研究了GDNF mRNA在妊娠期E11.5、E13.5和E18的胚胎大鼠、出生后P0和P10的新生大鼠和成年大鼠中枢神经系统和外周器官的发育表达。GDNF mRNA在整个中枢神经系统表达，在P0脊髓和P0和P10纹状体中表达水平最高。脑干（包括含有黑质DA神经元的腹侧中脑）、小脑、间脑和端脑以及从P7小脑制备的小脑颗粒细胞和从P1皮层制备的星形胶质细胞的原代培养物中存在较低水平。小脑具有不寻常的时间表达模式，在出生和成年时高，但在P10时无法检测到。GDNF: mRNA在许多外周组织中的表达水平也高于大脑。这些器官包括胚胎肢芽、肾脏和肠道；新生儿肾脏、肠道、肺和睾丸；以及成人的肺、肝和卵巢。除了预测的RT-PCR产物外，我们还观察到在成熟肽序列中显示与GDNF相同的小条带，但在前原蛋白序列中缺失了78个碱基对。这种缩短形式的GDNF mRNA具有与GDNF基本相同的分布模式，并且可能代表一种选择性剪接形式。从人胎儿星形胶质细胞中也扩增出同源的GDNF mRNA的短形式。这些观察结果表明，GDNF可能是其他类型中枢神经系统神经元以及黑质DA神经元的靶源和/或局部作用的神经营养因子。此外，GDNF可能作为外周神经系统的神经营养因子和/或作为非神经元细胞的生长因子发挥作用。
Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta family isolated from the rat glial tumor cell line, B49. In embryonic dopaminergic (DA) neurons in vitro, GDNF promotes survival, high-affinity dopamine uptake, and neurite outgrowth. We have used a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific to GDNF to study the developmental expression of GDNF mRNA in central nervous system (CNS) and peripheral organs of embryonic rat on gestational days E11.5, E13.5 and E18, neonatal rat on postnatal days P0 and P10, and adult rat. GDNF mRNA is expressed throughout the CNS, with highest levels in P0 spinal cord and in P0 and P10 striatum. Lower levels are present in the brainstem (including the ventral mesencephalon, which contains the DA neurons of the substantia nigra), cerebellum, diencephalon, and telencephalon, as well as in primary cultures of cerebellar granule cells prepared from P7 cerebellum and astrocytes prepared from P1 cortex. The cerebellum has an unusual temporal pattern of expression, high at birth and in the adult, but undetectable at P10. GDNF: mRNA is also expressed in many peripheral tissues at higher levels than in brain. These include embryonic limb bud, kidney and gut; neonatal kidney, gut, lung and testis; and adult lung, liver and ovary. In addition to the predicted RT-PCR product, we also observed a minor band which was shown to be identical to GDNF in the mature peptide sequence, but which has a 78 base pair deletion in the preproprotein sequence. This shortened form of GDNF mRNA has an essentially identical pattern of distribution as GDNF and may represent an alternatively spliced form. A homologous short form of GDNF mRNA was also amplified from human fetal astrocytes. These observations suggest that GDNF may be a target derived and/or locally acting neurotrophic factor for other classes of CNS neurons, as well as for DA neurons of the substantia nigra. Additionally, GDNF likely plays a role as a neurotrophic factor in the perpheral nervous system and/or serves as a growth factor for non-neuronal cells.