Uittenbogaard M, Peavy D R, Chiaramello A
Department of Anatomy and Cell Biology and Program of Neuroscience, George Washington University Medical Center, Washington, DC 20037, USA.
J Neurosci Res. 1999 Sep 15;57(6):770-81.
We report that the neuronal-specific basic helix-loop-helix (bHLH) gene NSCL-1 is expressed at multiple and distinct stages of cerebellar granule cell differentiation. During embryonic development, NSCI-1 expression is initially evenly distributed in the cerebellar primordium and then becomes restricted to the ventricular zone. At the early steps of granule cell development, NSCL-1 is not expressed in rhombic lip cells, but instead in migrating granule cell precursors. Its expression culminates during postnatal proliferation of the external germinal layer, and remains only transiently in the newly formed internal granular layer, and at a much lower level. Thus, NSCL-1 expression is linked to the onset of granule cell differentiation, but is not involved in the maintenance of the differentiated state. These findings suggest that NSCL-1 does not behave as a specification factor, but rather as a factor promoting expansion of progenitor external germinal layer (EGL) cells. Gel mobility shift assays show that NSCL-1 only binds DNA as a heterodimeric complex with the ME1a E-protein. We also provide the first evidence that NSCL-1 functions as a transcriptional activator when heterodimerized with the ME1a E-protein. Taken together, these results suggest that NSCL-1 participates in the regulatory network controlling gene expression during cerebellar granule cell differentiation.
我们报告称，神经元特异性碱性螺旋-环-螺旋（bHLH）基因NSCL-1在小脑颗粒细胞分化的多个不同阶段表达。在胚胎发育过程中，NSCI-1的表达最初均匀分布于小脑原基，随后局限于脑室区。在颗粒细胞发育的早期阶段，NSCL-1不在菱唇细胞中表达，而是在迁移的颗粒细胞前体中表达。其表达在生后外颗粒层增殖期间达到顶峰，并且仅在新形成的内颗粒层中短暂存在，且水平低得多。因此，NSCL-1的表达与颗粒细胞分化的起始相关，但不参与分化状态的维持。这些发现表明，NSCL-1并非作为一种特异性因子发挥作用，而是作为一种促进祖细胞外颗粒层（EGL）细胞扩增的因子。凝胶迁移率变动分析表明，NSCL-1仅作为与ME1a E蛋白形成的异二聚体复合物结合DNA。我们还提供了首个证据，即NSCL-1与ME1a E蛋白异二聚化时作为转录激活因子发挥作用。综上所述，这些结果表明，NSCL-1参与了小脑颗粒细胞分化过程中控制基因表达的调控网络。
