Yu Tian, Fotaki Vassiliki, Mason John O, Price David J
Centres for Integrative Physiology and Neuroscience Research, University of Edinburgh, Edinburgh, United Kingdom.
J Comp Neurol. 2009 Feb 10;512(5):613-27. doi: 10.1002/cne.21918.
The transcription factor Gli3 is expressed throughout developing telencephalon. Previous studies have focused on Gli3's role in dorsal telencephalon, which is greatly reduced in size in Gli3(Xt/Xt) mutants. We examined the effects of loss of Gli3 on early development of ventral telencephalon. Ventral telencephalon was defined in both wildtypes and Gli3(Xt/Xt) mutants on the basis of its expression of Olig2, Nkx2.1, Mash1, and Foxg1 and its lack of expression of Pax6. We found that at embryonic day (E)10.5 the volume of the ventral telencephalon is about 50% greater in Gli3(Xt/Xt) mutants than in wildtypes. By E12.5, however, the volume of the ventral telencephalon is about 20% lower in Gli3(Xt/Xt) mutants than in wildtypes. We observed a significant increase in the number of both apoptotic cells and newly differentiated neurons in the E10.5 Gli3(Xt/Xt) ventral telencephalon, suggesting that increased cell death and withdrawal of cells from the cell cycle might account for the failure of the Gli3(Xt/Xt) ventral telencephalon to grow normally by E12.5. We found no changes in the lengths of the cell cycles of proliferating ventral telencephalic cells at E10.5. We used marker analysis and optical projection tomography to assess the Gli3(Xt/Xt) forebrain in three dimensions and found that the Gli3(Xt/Xt) diencephalon is shifted relatively rostrally. We conclude that in the absence of Gli3 an abnormally large portion of the newly formed telencephalon is specified to a ventral fate but this then suffers impaired growth, due to defects of cell differentiation and death, contributing to severe distortion of the forebrain.
转录因子Gli3在整个端脑发育过程中均有表达。以往的研究主要聚焦于Gli3在背侧端脑中的作用，在Gli3(Xt/Xt)突变体中，背侧端脑的尺寸大幅减小。我们研究了Gli3缺失对腹侧端脑早期发育的影响。基于其Olig2、Nkx2.1、Mash1和Foxg1的表达以及Pax6的不表达，在野生型和Gli3(Xt/Xt)突变体中定义了腹侧端脑。我们发现，在胚胎第10.5天（E10.5），Gli3(Xt/Xt)突变体腹侧端脑的体积比野生型大约大50%。然而，到E12.5时，Gli3(Xt/Xt)突变体腹侧端脑的体积比野生型大约小20%。我们观察到E10.5的Gli3(Xt/Xt)腹侧端脑中凋亡细胞和新分化神经元的数量均显著增加，这表明细胞死亡增加和细胞退出细胞周期可能是Gli3(Xt/Xt)腹侧端脑到E12.5时未能正常生长的原因。我们发现E10.5时增殖的腹侧端脑细胞的细胞周期长度没有变化。我们使用标记分析和光学投影断层扫描对Gli3(Xt/Xt)前脑进行三维评估，发现Gli3(Xt/Xt)间脑相对向前移位。我们得出结论，在没有Gli3的情况下，新形成的端脑中异常大的一部分被指定为腹侧命运，但随后由于细胞分化和死亡缺陷而生长受损，导致前脑严重变形。
