Duncan M K, Bordas L, Dicicco-Bloom E, Chada K K
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
Dev Dyn. 1997 Jan;208(1):107-14. doi: 10.1002/(SICI)1097-0177(199701)208:1<107::AID-AJA10>3.0.CO;2-3.
Neurons throughout the central nervous system (CNS) undergo proliferation, migration, and differentiation during their histogenesis. Although numerous regulatory molecules are expressed in developing neurons, it is unknown whether most of these molecules have the same function throughout the CNS or play different roles in different neuronal populations. Previous studies have shown that Id-1 and NSCL-1 are expressed at high levels in the ventricular and subependymal zones, respectively, of the embryonic brain. In the present study, the expression of Id-1 and NSCL-1 was further investigated during postnatal development of the cerebellum. By Northern blot hybridization analysis, the expression levels of Id-1 and NSCL-1 mRNA were developmentally regulated in the cerebellum, with the highest mRNA levels coinciding with the time of maximal granule cell histogenesis. By in situ hybridization, NSCL-1 mRNA was found in the premigratory zone of the external granule layer (EGL), a structure developmentally analogous to the subependymal zone of the embryonic brain. In normal mice, Id-1 mRNA was found to be transiently expressed in the upper internal granule layer (IGL), a population of cells that recently completed their migration from the EGL. In the mouse mutant weaver, Id mRNA was only seen in granule cells that have reached their normal positions in the IGL. No Id-1 hybridization signal was observed in the large numbers of granule cells remaining in the EGL of weaver mice, indicating that Id-1 expression is controlled by spatial cues. The lack of Id-1 expression in ectopic weaver granule cells is compatible with previous suggestions of arrested differentiation. These results support the idea that transcriptional regulators of the helix-loop-helix gene family play important roles in neuronal development, exhibiting region-specific expression and function.
在整个中枢神经系统（CNS）中，神经元在其组织发生过程中经历增殖、迁移和分化。尽管在发育中的神经元中表达了众多调节分子，但尚不清楚这些分子中的大多数在整个中枢神经系统中是否具有相同的功能，或者在不同的神经元群体中发挥不同的作用。先前的研究表明，Id-1和NSCL-1分别在胚胎脑的脑室区和室管膜下区高水平表达。在本研究中，进一步研究了小脑出生后发育过程中Id-1和NSCL-1的表达。通过Northern印迹杂交分析，Id-1和NSCL-1 mRNA的表达水平在小脑中受到发育调控，最高的mRNA水平与颗粒细胞最大组织发生时间一致。通过原位杂交，在外部颗粒层（EGL）的迁移前区发现了NSCL-1 mRNA，该结构在发育上类似于胚胎脑的室管膜下区。在正常小鼠中，发现Id-1 mRNA在内部颗粒层上层（IGL）中短暂表达，这是一群最近从EGL完成迁移的细胞。在小鼠突变体weaver中，Id mRNA仅在已到达IGL中正常位置的颗粒细胞中可见。在weaver小鼠EGL中残留的大量颗粒细胞中未观察到Id-1杂交信号，表明Id-1表达受空间线索控制。异位weaver颗粒细胞中Id-1表达的缺乏与先前关于分化停滞的建议一致。这些结果支持了螺旋-环-螺旋基因家族的转录调节因子在神经元发育中起重要作用的观点，表现出区域特异性表达和功能。
