GSK3β controls the timing and pattern of the fifth spiral cleavage at the 24 cell stage in Lymnaea stagnalis
GSK3β controls the timing and pattern of the fifth spiral cleavage at the 24 cell stage in Lymnaea stagnalis
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GSK3β控制Lymnaea stagnalis 24细胞阶段第五次螺旋分裂的时间和模式
DOI：
10.1007/s00427-018-00625-1
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发表时间：
2019
影响因子：
2.4
通讯作者：
Kuroda R
中科院分区：
文献类型：
--
作者：
Takahashi H;Abe M;Kuroda R
通过初级体轴的确定和细胞命运的确定来建立多细胞生物的身体规划是生物学中的一个关键问题。我们检测了Wnt途径的三个组分gsk3β，β-catenin的基因定位，并研究了这些蛋白的四种选择性抑制剂对淡水蜗牛Lymneea(L.)螺旋卵裂胚胎早期发育的影响。Stagnalis.mRNAforgsk3、β和β-catenin在胚胎发育过程中均匀分布于胚胎各处，而杂乱的mRNAs则表现出特异性的定位，螺旋卵裂时卵裂球内和卵裂球间沿A-V轴的浓度存在差异。值得注意的是，通过对抑制剂的研究，我们发现了从2-细胞到4-细胞阶段的一个短暂的敏感期，在这段时间里，高度特异的1-氮杂苯丙酮(AZ)和氯化锂对GSK3β的抑制导致了随后的戏剧性的发育延迟和第五次卵裂(16-24细胞阶段)卵裂球的分裂模式的改变，导致了后期的外原肠形成和其他异常。抑制β-连环蛋白或脱发不起作用。我们的抑制实验确定了GSK3β在蜗牛胚胎的发育时机和定向细胞分裂中的新作用。还需要进一步的工作来确定该激酶的下游靶点。
Establishment of the body plan of multicellular organisms by the primary body axis determination and cell-fate specification is a key issue in biology. We have examined the mRNA localization of three Wnt pathway componentsgsk3β,β-catenin, anddisheveledand investigated the effects of four selective inhibitors of these proteins on the early developmental stages of the spiral cleavage embryo of the fresh water snailLymnaea (L.) stagnalis.mRNAs forgsk3βandβ-cateninwere distributed uniformly throughout the embryo during development whereasdisheveledmRNA showed specific localization with intra- and inter-blastomere differences in concentration along the A-V axis during spiral cleavages. Remarkably, through inhibitor studies, we identified a short sensitive period from the 2- to 4-cell stage in which GSK3β inhibition by the highly specific 1-azakenpaullone (AZ) and by LiCl induced a subsequent dramatic developmental delay and alteration of the cleavage patterns of blastomeres at the fifth cleavage (16- to 24-cell stage) resulting in exogastrulation and other abnormalities in later stages. Inhibition of β-Catenin or Disheveled had no effect. Our inhibitor experiments establish a novel role for GSK3β in the developmental timing and orientated cell division of the snail embryo. Further work will be needed to identify the downstream targets of the kinase.