DUAL ROLES OF THE RETINOBLASTOMA PROTEIN IN CELL-CYCLE REGULATION AND NEURON DIFFERENTIATION
DUAL ROLES OF THE RETINOBLASTOMA PROTEIN IN CELL-CYCLE REGULATION AND NEURON DIFFERENTIATION
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DOI：
10.1101/gad.8.17.2008
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发表时间：
1994-09-01
影响因子：
10.5
通讯作者：
HERRUP, K
中科院分区：
文献类型：
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作者：
LEE, EYHP;HU, NP;HERRUP, K
为了评估视网膜母细胞瘤蛋白(Rb)在正常发育过程中的功能，我们分析了缺乏视网膜母细胞瘤基因功能副本的小鼠胚胎(基因：Rb-1(Delta 20)/Rb-1(Delta 20))。我们的研究结果表明，Rb在神经细胞周期的调节中起着重要作用，在突变胚胎中，分裂细胞被发现远远超出了中枢和外周神经系统的正常神经起源区域。然而，除了异常的细胞周期调节外，突变胚胎还表现出两种不太预期的表型。首先，许多异位分裂的细胞在进入S期后不久就因凋亡而死亡。在感觉神经节中，大多数神经细胞通过这个过程死亡，与正常的靶相关神经元死亡大约在同一时间开始。其次，尽管某些分化标记物如N-CAM和BRN-3.0的表达似乎接近正常，但神经细胞，特别是感觉神经节中的神经细胞并不成熟。它们的形态发育不良，神经元βII微管蛋白的表达大大减少。TrkA、TrkB和低亲和力神经营养素受体p75(LNGFR)表达的优先降低可能与突变型胚胎中出现的神经细胞死亡和神经元分化不足有关。对来自晚期突变胚胎的背根和三叉神经节细胞进行原代培养，发现即使在适当的神经营养因子存在的情况下，神经元细胞的存活率和突起的生长也会减少。综上所述，这些结果表明，p110(Rb)蛋白不仅调节细胞周期的进程，而且对细胞的生存和分化也很重要。
To assess the functions of the retinoblastoma protein (RB) during normal development, we have analyzed mouse embryos that lack a functional copy of the retinoblastoma gene (genotype: Rb-1(Delta 20)/Rb-1(Delta 20)). Our findings demonstrate that RB plays an important role in the regulation of the neuronal cell cycle, In mutant embryos, dividing cells are found well outside of the normal neurogenic regions in both the central and peripheral nervous systems. In addition to abnormal cell cycle regulation, however, the mutant embryos show two less expected phenotypes. First, many of the ectopically dividing cells die by apoptosis shortly after their entrance into S phase. In sensory ganglia, most nerve cells die by this process, beginning at about the same time as normal target-related neuronal death. Second, although the expression of certain differentiation markers such as N-CAM and Brn-3.O appears to be near normal, nerve cells, especially in sensory ganglia, do not mature properly. Their morphology is stunted and expression of neuronal beta II tubulin is greatly reduced. Preferential reduction in the expression of TrkA, TrkB, and the low-affinity neurotrophin receptor p75(LNGFR) may be relevant to neuronal cell death and lack of neuronal differentiation seen in the mutant embryos. Primary cultures of dorsal root and trigeminal ganglion cells from later stage mutant embryos reveal a decrease in neuronal cell survival and in neurite outgrowth even in the presence of the appropriate neurotrophins. Taken together, these results suggest that the p110(RB) protein not only regulates progression through the cell cycle but is also important for cell survival and differentiation.