Zhang Q, Mason C A
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Dev Biol. 1998 Mar 1;195(1):75-87. doi: 10.1006/dbio.1997.8837.
In an in vitro model system based on purified target cerebellar granule neurons and explants of afferents, pontine mossy fiber afferents stop growing through contact-mediated mechanisms when they encounter granule neurons. Here we studied the developmental regulation of the stop signal posed by granule cells and the response of mossy fibers to the stop signal in two culture systems. Granule neurons presented in slices or as dissociated cells from postnatal day (P) 4 and P7 cerebellum were more potent in the arrest of P0 pontine neurites than younger (P0-P2) or older (up to P14) granule neurons. In contrast, pontine neurites at embryonic day (E) 18, during their period of normal growth toward the cerebellum, grew extensively on both cerebellar slices of all ages from P0 to P10 and dissociated P4 granule neurons. When E18 explants were maintained for 2 days before plating in medium conditioned by neonatal cerebellar cells, E18 pontine explants were rendered more responsive to the stop signal from P4 granule cells. These results indicate that the stop signal, and the response of afferents to it, are developmentally regulated. Moreover, factors within the target region may initiate these interactions.
在一个基于纯化的目标小脑颗粒神经元和传入神经外植体的体外模型系统中，脑桥苔藓纤维传入神经在遇到颗粒神经元时，会通过接触介导机制停止生长。在此，我们在两种培养系统中研究了颗粒细胞发出的停止信号的发育调控以及苔藓纤维对该停止信号的反应。与较年轻（P0 - P2）或较年长（直至P14）的颗粒神经元相比，来自出生后第（P）4天和P7天小脑的切片或解离细胞形式的颗粒神经元在阻止P0脑桥神经突生长方面更有效。相比之下，胚胎第（E）18天的脑桥神经突在向小脑正常生长期间，在从P0到P10的所有年龄段的小脑切片以及解离的P4颗粒神经元上都广泛生长。当E18外植体在接种到新生小脑细胞条件培养基中培养2天后再进行铺板时，E18脑桥外植体对来自P4颗粒细胞的停止信号反应更强。这些结果表明，停止信号以及传入神经对其反应受到发育调控。此外。靶区域内的因子可能启动这些相互作用。
