McDougall Alex, Chenevert Janet, Lee Karen W, Hebras Celine, Dumollard Remi
Developmental Biology Unit UMR 7009, UMPC Univ. Paris 06 and Center National de la Recherche (CNRS), Observatoire Océanologique, 06230 Villefranche-sur-Mer, France.
Results Probl Cell Differ. 2011;53:153-69. doi: 10.1007/978-3-642-19065-0_8.
In ascidians the cell cycle machinery has been studied mainly in oocytes while ascidian embryos have been used to dissect the mechanism that controls asymmetric cell division (ACD). Here we overview the most specific and often exceptional points and events in cell cycle control in ascidian oocytes and early embryos. Mature stage IV eggs are arrested at metaphase I due to cytostatic factor (CSF). In vertebrates, unfertilized eggs are arrested at metaphase II by CSF. Meta II-CSF is mediated by the Mos/MEK/MAPK/Erp1 pathway, which inhibits the ubiquitin ligase APC/C(cdc20) preventing cyclin B destruction thus stabilizing MPF activity. CSF is inactivated by the fertilization Ca(2+) transient that stimulates the destruction of Erp1 thus releasing APC/C(cdc20) from inhibition. Although many of the components of CSF are conserved between the ascidian and the vertebrates, the lack of Erp1 in the ascidians (and indeed other invertebrates) is notable since the Mos/MAPK pathway nonetheless mediates Meta I-CSF. Moreover, since the fertilization Ca(2+) transient targets Erp1, it is not clear how the sperm-triggered Ca(2+) transient in ascidians (and again other invertebrates) stimulates cyclin B destruction in the absence of Erp1. Nonetheless, like mammalian eggs, sperm trigger a series of Ca(2+) oscillations that increases the rate of cyclin B destruction and the subsequent loss of MAPK activity leading to meiotic exit in ascidians. Positive feedback from MPF maintains the Ca(2+) oscillations in fertilized ascidian eggs ensuring the eventual loss of MPF stimulating the egg-to-embryo transition. Embryonic cell cycles in the ascidian are highly stereotyped where both the rate of cell division and the orientation of cell division planes are precisely controlled. Three successive rounds of ACD generate two small posterior germ cell precursors at the 64 cell stage. The centrosome-attracting body (CAB) is a macroscopic cortical structure visible by light microscopy that causes these three rounds of ACD. Entry into mitosis activates the CAB causing the whole mitotic spindle to rotate and migrate toward the cortical CAB leading to a highly ACD whereby one small cell is formed that inherits the CAB and approximately 40 maternal postplasmic/PEM RNAs including the germ cell marker vasa.
在海鞘中，细胞周期机制主要是在卵母细胞中进行研究的，而海鞘胚胎则被用于剖析控制不对称细胞分裂（ACD）的机制。在此，我们概述海鞘卵母细胞和早期胚胎细胞周期控制中最具特异性且常常异常的要点和事件。成熟的IV期卵由于细胞静止因子（CSF）而停滞在减数第一次分裂中期。在脊椎动物中，未受精的卵通过CSF停滞在减数第二次分裂中期。减数第二次分裂CSF由Mos/MEK/MAPK/Erp1通路介导，该通路抑制泛素连接酶APC/C（cdc20），阻止细胞周期蛋白B的降解，从而稳定MPF活性。受精时的Ca(2+)瞬变使CSF失活，刺激Erp1的降解，从而使APC/C（cdc20）从抑制状态中释放出来。尽管海鞘和脊椎动物之间CSF的许多成分是保守的，但海鞘（以及其他无脊椎动物）中缺乏Erp1是值得注意的，因为Mos/MAPK通路仍然介导减数第一次分裂CSF。此外，由于受精时的Ca(2+)瞬变作用于Erp1，目前尚不清楚海鞘（以及其他无脊椎动物）中精子触发的Ca(2+)瞬变在缺乏Erp1的情况下如何刺激细胞周期蛋白B的降解。尽管如此，与哺乳动物的卵一样，精子触发一系列Ca(2+)振荡，增加细胞周期蛋白B的降解速率以及随后MAPK活性的丧失，从而导致海鞘减数分裂退出。MPF的正反馈维持受精海鞘卵中的Ca(2+)振荡，确保MPF最终丧失，刺激卵向胚胎的转变。海鞘中的胚胎细胞周期具有高度的模式化，细胞分裂速率和细胞分裂平面的方向都受到精确控制。三轮连续的ACD在64细胞阶段产生两个小的后部生殖细胞前体。中心体吸引体（CAB）是一种通过光学显微镜可见的宏观皮质结构，它引发这三轮ACD。进入有丝分裂会激活CAB，导致整个有丝分裂纺锤体旋转并向皮质CAB迁移，从而导致高度不对称的细胞分裂，形成一个继承CAB和大约40种母体胞质后/ PEM RNA（包括生殖细胞标记物vasa）的小细胞。
