Simons Initiative for the Developing Brain, Biomedical Sciences, The University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
eNeuro. 2018 Oct 23;5(5). doi: 10.1523/ENEURO.0367-18.2018. eCollection 2018 Sep-Oct.
Our aim was to study the mechanisms that contribute to the development of discrete thalamic nuclei during mouse embryogenesis (both sexes included). We characterized the expression of the transcription factor coding gene and the distribution of cells that expressed in their lineage. We used genetic fate mapping to show that -lineage cells mainly contribute to a subset of thalamic nuclei, in particular the lateral geniculate nuclei (LGNs), which are crucial components of the visual pathway. We observed that almost all -lineage diencephalic progenitors express the transcription factor Pax6 at variable location-dependent levels. We used conditional mutagenesis to delete either one or both copies of from -lineage cells. We found that -lineage cells carrying either homozygous or heterozygous loss of contributed in abnormally high numbers to one or both of the main lateral geniculate nuclei (LGNs). This could not be attributed to a change in cell production and was likely due to altered sorting of thalamic cells. Our results indicate that positional information encoded by the levels of Pax6 in diencephalic progenitors is an important determinant of the eventual locations of their daughter cells.
我们的目的是研究在小鼠胚胎发生过程中（包括雌雄两性）导致离散丘脑核发育的机制。我们描述了转录因子编码基因 的表达模式和表达 的细胞在其谱系中的分布。我们利用遗传命运图谱显示 - 谱系细胞主要贡献于丘脑核的一个子集，特别是外侧膝状体核（LGN），其是视觉通路的关键组成部分。我们观察到，几乎所有 - 谱系神经上皮前体细胞在不同位置依赖的水平上以可变的方式表达转录因子 Pax6。我们利用条件性突变使 - 谱系细胞中的一个或两个 拷贝缺失。我们发现携带 纯合或杂合缺失的 - 谱系细胞异常大量地贡献于一个或两个主要的外侧膝状体核（LGN）。这不能归因于细胞产生的变化，很可能是由于丘脑细胞的分选发生改变。我们的结果表明，神经上皮前体细胞中 Pax6 水平编码的位置信息是决定其子细胞最终位置的重要决定因素。
