ROLES OF FIBROBLAST GROWTH FACTOR (B-FGF) AND GAP JUNCTION ON NEOCORTICAL HISTOGENESIS

我们研究了用FGF-2或1-辛醇培养的外植体的细胞周期进程。FGF-2是新生皮层pve的生理性丝裂原的代表。另一方面，1-辛醇已被证明通过间隙连接阻断介导抗丝裂作用。在体内，有丝分裂后的细胞有两种选择，要么退出周期并迁移出VZ（宿命到Q段），要么重新进入S期并继续循环（宿命到P段）。相比之下，在外植体中，有相当大比例的外植体没有做出这两种选择，而是以不确定的状态（I分数）持续存在于VZ中。这种现象被FGF-2和1-辛醇以相反的方向和不同的程度调制。这些有丝分裂和抗有丝分裂药物的调节仅在神经遗传梯度的较高级区域观察到。这种现象是一种相对选择性的现象，因为上皮的大多数其他重要特性几乎没有改变：上皮保持其结构完整性，并且没有中断相互运动的核迁移，尊重细胞周期阶段。此外，在普遍低发生率的固缩没有增加。也就是说，这些培养条件似乎揭示了相对选择性地调节PVE细胞增殖命运的机制。重要的是，FGF-2或1-辛醇调节这种作用的机制显然是受发育调控的，仅在神经遗传梯度的相对高级区域表达。

We have examined the cell cycle progression in explants cultured with FGF-2 or 1-octanol. FGF-2 is representative of physiologic mitogens respecting the neocortical PVE.1-octanol, on the other hand, has been demonstrated to mediate a countering antimitogenic effect through gap junction blockade.In vivo, there are two options for postmitotic cells, either to exit the cycle and migrate out of the VZ (fate to Q fraction) or to re-enter S phase and continue to cycle (fate to P fraction). In the explants, by contrast, a substantial proportion makes neither of these choices but instead persists in the VZ in an indeterminate state (I fraction). The phenomenon is modulated, in opposing directions and to different degree, by FGF-2 and 1-octanol. Modulation by these mitogenic and antimitogenic agents is observed only in the more advanced region of the neurogenetic gradient. The phenomenon is a relatively selective one in that the majority of other vital properties of the epithelium are little altered : the epithelium maintains its architectonic integrity and there is no interruption of interkinetic nuclear migration, respecting cell cycle phases. Moreover, there is no augmentation in the generally low occurrence rate of pyknosis. That is, these conditions of culture appear to have unmasked relatively selectively mechanisms regulatory to the proliferative fates of cells of the PVE.Importantly, mechanisms by which this effect is modulated by FGF-2 or 1-octanol are evidently developmentally regulated, expressed only in the relatively advanced region of the neurogenetic gradient.