Segal R A, Pomeroy S L, Stiles C D
Department of Cell and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Neurosci. 1995 Jul;15(7 Pt 1):4970-81. doi: 10.1523/JNEUROSCI.15-07-04970.1995.
In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth.
在发育中的小脑里，外颗粒层的年轻颗粒神经元对脑源性神经营养因子（BDNF）反应更为优先，而小脑内部的成熟神经元则对神经营养因子3（NT3）反应更为优先。我们在此表明，这种解剖学上的差异反映了神经营养因子受体基因表达水平上一个受发育调控的转换。发育转换的显著特征是编码功能性BDNF和NT3受体酪氨酸激酶的mRNA转录本比例的变化。BDNF受体trkB与NT3受体trkC的比例从新生小脑的5:1逆转至成年小脑的1:3。TrkB和TrkC是密切相关的跨膜酪氨酸蛋白激酶。然而，小脑颗粒神经元中BDNF和NT3受体的激活并不会产生同等的生物学反应。在聚集细胞培养和单细胞试验中，BDNF通过影响神经突伸长来增强早期颗粒细胞的轴突生长。相比之下，NT3则改变了轴突生长的形态。总体而言，这些发现表明，小脑发育过程中神经营养因子受体的调控对于轴突生长的时间和形态很重要。
