Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, United States of America.
PLoS One. 2012;7(10):e47111. doi: 10.1371/journal.pone.0047111. Epub 2012 Oct 4.
Unlike the laminar arrangement of neurons in the neocortex, thalamic neurons aggregate to form about dozens of nuclei, many of which make topographic connections with specific areas in the neocortex. The molecular mechanisms underlying the formation of thalamic nuclei remain largely unknown. Homeodomain transcription factor Gbx2 is specifically expressed in the developing thalamus. Deleting Gbx2 leads to severe disruption of the histogenesis of the thalamus in mice, demonstrating an essential role of Gbx2 in this brain structure. Using inducible genetic fate mapping, we have previously shown that the neuronal precursors for different sets of thalamic nuclei have distinctive onset and duration of Gbx2 expression, suggesting that the dynamic expression of Gbx2 plays an important role in the specification and differentiation of thalamic nuclei. Here, we showed that the Gbx2 lineage exclusively gives rise to neurons but not glia in the thalamus. We performed conditional deletion to examine the temporal requirements of Gbx2 in the developing thalamus in mice. Corresponding to the dynamic and differential expression of Gbx2 in various thalamic nucleus groups, deleting Gbx2 at different embryonic stages disrupts formation of distinct sets of thalamic nuclei. Interestingly, different thalamic nuclei have remarkably different requirements of Gbx2 for the survival of thalamic neurons. Furthermore, although Gbx2 expression persists in many thalamic nuclei until adulthood, only the initial expression of Gbx2 following neurogenesis is crucial for the differentiation of thalamic nuclei. Our results indicate that the dynamic expression of Gbx2 may act as an important determinant in coupling with other developmental programs to generate distinct thalamic nuclei.
与新皮层中的神经元层状排列不同，丘脑神经元聚集形成大约几十个核，其中许多与新皮层的特定区域形成拓扑连接。丘脑核形成的分子机制在很大程度上仍然未知。同源结构域转录因子 Gbx2 特异性表达于发育中的丘脑。删除 Gbx2 会导致小鼠丘脑的组织发生严重破坏，表明 Gbx2 在这个脑结构中具有重要作用。使用诱导性遗传命运图谱，我们之前已经表明，不同丘脑核组的神经元前体具有不同的 Gbx2 表达起始和持续时间，这表明 Gbx2 的动态表达在丘脑核的特化和分化中发挥重要作用。在这里，我们表明 Gbx2 谱系仅在丘脑中转导神经元而不是胶质细胞。我们进行了条件性缺失，以检查 Gbx2 在小鼠发育中的丘脑中的时间要求。与 Gbx2 在各种丘脑核群中的动态和差异表达相对应，在不同的胚胎阶段删除 Gbx2 会破坏不同的丘脑核组的形成。有趣的是，不同的丘脑核对 Gbx2 存在明显不同的生存要求。此外，尽管 Gbx2 表达在许多丘脑核中持续到成年期，但只有神经发生后的 Gbx2 初始表达对于丘脑核的分化是至关重要的。我们的结果表明，Gbx2 的动态表达可能作为与其他发育程序偶联的重要决定因素，以产生不同的丘脑核。
