Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development
Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development
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DOI：
10.1093/cercor/bhw187
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发表时间：
2017-07-01
期刊：
影响因子：
3.7
通讯作者：
Kawasaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Ebisu, Haruka;Iwai-Takekoshi, Lena;Kawasaki, Hiroshi
丘脑在发育过程中形成的分子机制已被深入研究。虽然区分丘脑原基与邻近脑结构的转录因子已经被发现，但那些参与丘脑内模式化的转录因子在很大程度上还不清楚。在这里，我们表明，Foxp2，叉头转录因子家族的成员，调节丘脑发育过程中的图案。我们发现Foxp2在小鼠胚胎的丘脑原基中呈梯度表达模式。Foxp2在丘脑原基后部表达量高，前部表达量低。在Foxp2（R552H）基因敲入小鼠，其中有一个错义功能丧失突变的叉头域Foxp2，丘脑核的后区的丘脑萎缩，而中间区域的扩大。一致地，Foxp2（R552H）敲入小鼠表现出丘脑皮质投射模式的变化。我们的研究结果揭示了Foxp2在发育过程中丘脑图案化和丘脑皮质投射中的重要作用。
The molecular mechanisms underlying the formation of the thalamus during development have been investigated intensively. Although transcription factors distinguishing the thalamic primordium from adjacent brain structures have been uncovered, those involved in patterning inside the thalamus are largely unclear. Here, we show that Foxp2, a member of the forkhead transcription factor family, regulates thalamic patterning during development. We found a graded expression pattern of Foxp2 in the thalamic primordium of the mouse embryo. The expression levels of Foxp2 were high in the posterior region and low in the anterior region of the thalamic primordium. In Foxp2 (R552H) knockin mice, which have a missense loss-of-function mutation in the forkhead domain of Foxp2, thalamic nuclei of the posterior region of the thalamus were shrunken, while those of the intermediate region were expanded. Consistently, Foxp2 (R552H) knockin mice showed changes in thalamocortical projection patterns. Our results uncovered important roles of Foxp2 in thalamic patterning and thalamocortical projections during development.