The molecular basis of defective lens development in the Iberian mole.

The molecular basis of defective lens development in the Iberian mole.
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DOI:
10.1186/1741-7007-6-44
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发表时间:
2008-10-21
期刊:
影响因子:
5.4
通讯作者:
Collinson, J. Martin
Collinson, J. Martin
中科院分区:
生物学2区
文献类型:
--
作者:
Carmona, F. David;Jimenez, Rafael;Collinson, J. Martin

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化石哺乳动物面临的自然选择压力与那些作用于表面居住动物的压力不同,这些压力可能导致视觉系统发育减少。我们研究了一种真正的鼹鼠,伊比利亚鼹鼠Talpa occurentalis的眼睛发育,并提出了异常透镜发展的分子基础。这是第一次在分子水平上对任何穴居哺乳动物的眼睛进行胚胎发育研究。伊比利亚鼹鼠的透镜纤维分化尚未完成。虽然眼睛发育开始正常(类似于其他模式物种),缺陷后,透镜囊泡关闭。PAX 6在发育中的透镜纤维核中不下调,如在其他物种中一样,并且在一些但不是所有透镜纤维中存在FOXE 3(PAX 6的推定下游效应物)的异位表达。FOXE 3阳性透镜纤维在胚胎透镜的后室中继续增殖,但与小鼠不同的是,在出生后的鼹鼠透镜中任何地方都没有检测到增殖。前上皮细胞的未分化状态受到损害,其中大多数发生凋亡。此外,β-晶体蛋白和PROX 1的表达模式是异常的,我们的数据表明,在伊比利亚鼹鼠中编码β-晶体蛋白的基因不直接受PAX 6,c-MAF和PROX 1的调节,因为它们在其他模式脊椎动物中。在其他模式脊椎动物中,控制透镜发育的遗传途径将透镜有力地划分为简单的、未分化的、增殖的前上皮和静止的、无核的、终末分化的后透镜纤维。这些途径在葡萄胎中不那么强,并导致前上皮表型的丧失和透镜纤维的仅部分分化,其继续表达“上皮”基因。在其他脊椎动物中形成的遗传调控网络的范例似乎并不适用于伊比利亚鼹鼠。
Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian mole Talpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryological developmental study of the eyes of any fossorial mammal at the molecular level. Lens fibre differentiation is not completed in the Iberian mole. Although eye development starts normally (similar to other model species), defects are seen after closure of the lens vesicle. PAX6 is not down-regulated in developing lens fibre nuclei, as it is in other species, and there is ectopic expression of FOXE3, a putative downstream effector of PAX6, in some, but not all lens fibres. FOXE3-positive lens fibres continue to proliferate within the posterior compartment of the embryonic lens, but unlike in the mouse, no proliferation was detected anywhere in the postnatal mole lens. The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis. Furthermore, β-crystallin and PROX1 expression patterns are abnormal and our data suggest that genes encoding β-crystallins are not directly regulated by PAX6, c-MAF and PROX1 in the Iberian mole, as they are in other model vertebrates. In other model vertebrates, genetic pathways controlling lens development robustly compartmentalise the lens into a simple, undifferentiated, proliferative anterior epithelium, and quiescent, anuclear, terminally differentiated posterior lens fibres. These pathways are not as robust in the mole, and lead to loss of the anterior epithelial phenotype and only partial differentiation of the lens fibres, which continue to express 'epithelial' genes. Paradigms of genetic regulatory networks developed in other vertebrates appear not to hold true for the Iberian mole.
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