LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis.
LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis.
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DOI：
10.1523/jneurosci.4216-12.2013
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发表时间：
2013-04-17
期刊：
影响因子：
--
通讯作者：
Tole S
中科院分区：
文献类型：
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作者：
Roy A;de Melo J;Chaturvedi D;Thein T;Cabrera-Socorro A;Houart C;Meyer G;Blackshaw S;Tole S
眼睛的形成是由一个复杂的网络眼场转录因子（EFTFs），包括LIM同源结构域基因Lhx 2的调节。我们在小鼠中使用条件性敲除策略在此过程中的不同阶段破坏Lhx 2功能。我们发现，Lhx 2的功能是需要在一个持续的方式，以保持跨多个阶段的视觉身份，从视泡的形成到神经视网膜的分化。在每个阶段Lhx 2的损失导致一组分子标记物的上调，这些分子标记物通常在视泡或视网膜的一部分中的丘脑隆起和前背侧下丘脑中表达。此外，Lhx 2功能维持的时间越长，光学形态发生的进展越大。早期功能丧失导致整个端脑-视-下丘脑区域的严重错误模式，使得视泡位置错误，似乎是从间脑-端脑边界（DTB）产生的。在随后的阶段，Lhx 2的损失并不影响视泡的位置，但引起视杯形成的逮捕。如果从E11.5开始Lhx 2在神经视网膜中被选择性地破坏，则神经视网膜显示出明显的畸形沿着丘脑隆起和前背侧下丘脑特异性标志物的异常表达。我们的研究结果表明，在整个光学发育的早期阶段，Lhx 2的持续需求，不仅要保持光学身份抑制替代的命运，但也调解多个步骤的光学形态。这些研究结果提供了新的见解的无眼表型的Lhx 2突变体，并揭示了新的作用，这种转录因子在眼睛的发展。
Eye formation is regulated by a complex network of eye field transcription factors (EFTFs) including LIM-homeodomain gene Lhx2. We disrupted Lhx2 function at different stages during this process using a conditional knockout strategy in mice. We find that Lhx2 function is required in an ongoing fashion to maintain optic identity across multiple stages, from the formation of the optic vesicle to the differentiation of the neuroretina. At each stage loss of Lhx2 led to upregulation of a set of molecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamus in a portion of the optic vesicle or retina. Furthermore, the longer Lhx2 function was maintained, the further optic morphogenesis progressed. Early loss of function caused profound mispatterning of the entire telencephalic-optic-hypothalamic field, such that the optic vesicle became mispositioned and appeared to arise from the diencephalic-telencephalic boundary (DTB). At subsequent stages, loss of Lhx2 did not affect optic vesicle position, but caused arrest of optic cup formation. If Lhx2 was selectively disrupted in the neuroretina from E11.5, the neuroretina showed gross dysmorphology along with aberrant expression of markers specific to the thalamic eminence and anterodorsal hypothalamus. Our findings indicate a continual requirement for Lhx2 throughout the early stages of optic development, not only to maintain optic identity by suppressing alternative fates, but also to mediate multiple steps of optic morphogenesis. These findings provide new insight into the anophthalmic phenotype of the Lhx2 mutant and reveal novel roles for this transcription factor in eye development.