Zic4-Lineage Cells Increase Their Contribution to Visual Thalamic Nuclei during Murine Embryogenesis If They Are Homozygous or Heterozygous for Loss of Pax6 Function.
Zic4-Lineage Cells Increase Their Contribution to Visual Thalamic Nuclei during Murine Embryogenesis If They Are Homozygous or Heterozygous for Loss of Pax6 Function.
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DOI：
10.1523/eneuro.0367-18.2018
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发表时间：
2018-09
期刊：
影响因子：
3.4
通讯作者：
Price DJ
中科院分区：
文献类型：
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作者：
Li Z;Pratt T;Price DJ
我们的目的是研究在小鼠胚胎发生(包括两性)过程中促进丘脑离散核发育的机制。我们鉴定了转录因子编码基因Zic4的表达以及表达Zic4的细胞在其谱系中的分布。我们使用遗传命运图谱显示，Zic4系细胞主要贡献丘脑核团的一个子集，特别是外侧膝状核(LGNs)，这是视觉通路的关键组成部分。我们观察到，几乎所有Zic4系间脑祖细胞都以不同的位置依赖水平表达转录因子Pax6。我们使用条件突变从Zic4系细胞中删除了Pax6的一个或两个拷贝。我们发现，携带Pax6纯合子或杂合子缺失的Zic4系细胞在一个或两个主要外侧膝状核(LGNs)中贡献了异常高的数量。这不能归因于细胞产量的变化，而可能是由于丘脑细胞分类的改变。我们的结果表明，由间脑祖细胞中Pax6水平编码的位置信息是其子代细胞最终位置的重要决定因素。
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 Zic4 and the distribution of cells that expressed Zic4 in their lineage. We used genetic fate mapping to show that Zic4-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 Zic4-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 Pax6 from Zic4-lineage cells. We found that Zic4-lineage cells carrying either homozygous or heterozygous loss of Pax6 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.