Widenfalk J, Nosrat C, Tomac A, Westphal H, Hoffer B, Olson L
Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
J Neurosci. 1997 Nov 1;17(21):8506-19. doi: 10.1523/JNEUROSCI.17-21-08506.1997.
Cloning strategies were used to identify a gene termed glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta) related to GDNFR-alpha. In situ hybridization was then used to map cellular expression of the GDNF-related trophic factor neurturin (NTN) and GDNFR-beta mRNA in developing and adult mice, and comparisons with GDNFR-alpha and RET were made. Neurturin is expressed in postnatal cerebral cortex, striatum, several brainstem areas, and the pineal gland. GDNFR-beta mRNA was more widely expressed in the developing and adult CNS, including cerebral cortex, cerebellum, thalamus, zona incerta, hypothalamus, brainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves. NTN colocalized with RET and GDNFR-alpha in ureteric buds of the developing kidney. The circular muscle layer of the developing intestines, smooth muscle of the urether, and developing bronchiolae also expressed NTN. GDNFR-beta was found in myenteric but not submucosal intestinal plexuses. In developing salivary glands NTN had an epithelial expression, whereas GDNFR-beta was expressed in surrounding tissue. Neurturin and GDNFR-beta were present in developing sensory organs. In the gonads, NTN appeared to be expressed in Sertoli cells and in the epithelium of the oviduct, whereas GDNFR-beta was expressed by the germ cell line. Our findings suggest multiple roles for NTN and GDNFR-beta in the developing and adult organism. Although NTN and GDNFR-beta expression patterns are sometimes complementary, this is not always the case, suggesting multiple modi operandi of GDNF and NTN in relation to RET and the two binding proteins, GDNFR-alpha and GDNFR-beta.
采用克隆策略鉴定出一个与胶质细胞系源性神经营养因子受体α（GDNFR-α）相关的基因，命名为胶质细胞系源性神经营养因子受体β（GDNFR-β）。随后运用原位杂交技术，在发育中和成年小鼠体内定位胶质细胞系源性神经营养因子相关营养因子神经营养素（NTN）和GDNFR-β mRNA的细胞表达情况，并与GDNFR-α和RET进行比较。神经营养素在出生后的大脑皮层、纹状体、几个脑干区域以及松果体中表达。GDNFR-β mRNA在发育中和成年中枢神经系统中表达更为广泛，包括大脑皮层、小脑、丘脑、未定带、下丘脑、脑干和脊髓，以及感觉神经元亚群和发育中的外周神经。NTN在发育中肾脏的输尿管芽中与RET和GDNFR-α共定位。发育中肠道的环形肌层、输尿管平滑肌和发育中的细支气管也表达NTN。在肌间神经丛而非黏膜下肠神经丛中发现了GDNFR-β。在发育中的唾液腺中，NTN呈上皮表达，而GDNFR-β在周围组织中表达。神经营养素和GDNFR-β存在于发育中的感觉器官中。在性腺中，NTN似乎在支持细胞和输卵管上皮中表达，而GDNFR-β由生殖细胞系表达。我们的研究结果表明，NTN和GDNFR-β在发育中和成年生物体中具有多种作用。尽管NTN和GDNFR-β的表达模式有时互补，但情况并非总是如此，这表明胶质细胞系源性神经营养因子（GDNF）和NTN与RET以及两种结合蛋白GDNFR-α和GDNFR-β存在多种作用方式。
