Transcription Factor Foxd1 Is Required for the Specification of the Temporal Retina in Mammals
Transcription Factor Foxd1 Is Required for the Specification of the Temporal Retina in Mammals
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DOI：
10.1523/jneurosci.0394-11.2011
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发表时间：
2011-04-13
影响因子：
5.3
通讯作者：
Herrera, Eloisa
中科院分区：
文献类型：
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作者：
Isabel Carreres, Maria;Escalante, Augusto;Herrera, Eloisa
视觉系统的组织在鸟类和哺乳动物中是不同的。在这两种情况下，视网膜轴突的投影地形的视觉目标在大脑中，但在鸟类的视觉纤维从整个视网膜交叉的视交叉，在哺乳动物中，一些轴突从颞视网膜分歧的中线，以项目同侧。鸡的功能获得实验提出了转录因子Foxd1指定视网膜时间特性的假设。然而，目前还不清楚Foxd1是否是这个功能所必需的。在哺乳动物中，Foxd 1在视交叉区域的图案形成中的关键作用使其在视网膜中的细胞自主功能的解释变得复杂。此外，针对Foxd 1鉴定的靶分子在鸡和小鼠中是不同的，导致对Foxd 1在哺乳动物中的功能的质疑。在这里，我们表明，在小鼠中，Foxd1的印记在视网膜中的时间功能，如轴突同侧和头侧的目标，在丘区和EphA6是Foxd1的下游效应器，发送颞轴突的头侧丘。此外，我们的数据支持这样一种模型，其中EphA6通过顺式ephrinA5的脱敏对于EphA6的正常功能不是必需的。总的来说，这些结果表明，Foxd1作为一个保守的时间身份决定因素的功能，但揭示了下游效应，并可能其作用机制，在哺乳动物和鸟类是不同的。
The organization of the visual system is different in birds and mammals. In both, retinal axons project topographically to the visual targets in the brain; but whereas in birds visual fibers from the entire retina decussate at the optic chiasm, in mammals, a number of axons from the temporal retina diverge at the midline to project ipsilaterally. Gain-of-function experiments in chick raised the hypothesis that the transcription factor Foxd1 specifies retinal temporal identity. However, it remains unknown whether Foxd1 is necessary for this function. In mammals, the crucial role of Foxd1 in the patterning of the optic chiasm region has complicated the interpretation of its cell-autonomous function in the retina. Furthermore, target molecules identified for Foxd1 are different in chicks and mice, leading to question the function of Foxd1 in mammals. Here we show that in the mouse, Foxd1 imprints temporal features in the retina such as axonal ipsilaterality and rostral targeting in collicular areas and that EphA6 is a Foxd1 downstream effector that sends temporal axons to the rostral colliculus. In addition, our data support a model in which the desensitization of EphA6 by ephrinA5 in cis is not necessary for the proper functioning of EphA6. Overall, these results indicate that Foxd1 functions as a conserved determinant of temporal identity but reveal that the downstream effectors, and likely their mechanisms of action, are different in mammals and birds.