Foxd1 is required for proper formation of the optic chiasm
Foxd1 is required for proper formation of the optic chiasm
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DOI：
10.1242/dev.01431
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Mason, C
中科院分区：
文献类型：
--
作者：
Herrera, E;Marcus, R;Mason, C
在具有双眼视觉的动物中，来自每只眼睛的视网膜神经节细胞（RGC）轴突在发育中的腹侧间脑中分类以投射到同侧或对侧目标，从而形成视交叉。同侧投射的轴突来自腹颞（VT）视网膜和对侧投射的轴突主要来自其他视网膜象限。翼状螺旋转录因子Foxd 1（以前称为BF-2，脑因子2）在VT视网膜中表达，以及在视交叉形成期间在腹侧间脑中表达。我们在这里报告说，在胚胎缺乏Foxd 1，视网膜发育和交叉形态发生中断。在Foxd 1缺陷的视网膜中，指定同侧投射的蛋白质，如Zic 2和EphB 1，缺失，并且Foxg 1（BF-1）的结构域从鼻视网膜扩展到VT新月形。在视网膜-视交叉共培养物中，来自Foxd 1缺陷型视网膜的VT RGCs不被视交叉细胞排斥，并且在体内许多VT RGCs异常地向对侧投射。然而，即使同侧程序在视网膜中丢失，在Foxd 1缺陷的胚胎中也会产生比正常的未杂交组件更大的组件。视交叉缺陷包括视交叉中的轴突停滞和投射到视束的RGC总数的减少。此外，在Foxd 1缺陷的腹侧间脑中，Foxg 1侵入Foxd 1结构域，Zic 2和Islet 1表达最小化，Slit 2过早扩张，这些变化可能导致轴突投射错误。因此，Foxd 1在建立双眼视觉通路中起着双重作用：第一，在VT视网膜的规范中，作用于指导同侧通路的蛋白质的上游;第二，在视交叉形成的发育中的腹侧间脑的图案化中。
In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye sort in the developing ventral diencephalon to project to ipsi- or contralateral targets, thereby forming the optic chiasm. Ipsilaterally projecting axons arise from the ventrotemporal (VT) retina and contralaterally projecting axons primarily from the other retinal quadrants. The winged helix transcription factor Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as well as in the ventral diencephalon during the formation of the optic chiasm. We report here that in embryos lacking Foxd1, both retinal development and chiasm morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-chiasm co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by chiasm cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even though the ipsilateral program is lost in the retina, a larger than normal uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include axon stalling in the chiasm and a reduction in the total number of RGCs projecting to the optic tract. In addition, in the Foxd1 deficient ventral diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are minimized, and Slit2 prematurely expands, changes that could contribute to axon projection errors. Thus, Foxd1 plays a dual role in the establishment of the binocular visual pathways: first, in specification of the VT retina, acting upstream of proteins directing the ipsilateral pathway; and second, in the patterning of the developing ventral diencephalon where the optic chiasm forms.