The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.
The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.
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DOI：
10.1007/s00429-014-0740-x
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发表时间：
2015
影响因子：
3.1
通讯作者：
Rath MF
中科院分区：
文献类型：
--
作者：
Yamazaki F;Møller M;Fu C;Clokie SJ;Zykovich A;Coon SL;Klein DC;Rath MF
Lhx9是LIM同源异型盒基因家族的成员。在哺乳动物胚胎发育过程中，它在包括松果体在内的大脑中表达。由于性腺发育失败，Lhx9基因缺失会导致不育。目前的研究是为了研究松果体中的Lhx9生物学。Lhx9在发育中的大鼠松果体中高度表达，转录丰度在发育早期达到峰值；成年后转录水平下降到几乎检测不到的水平，这种时间模式通常与Lhx9在其他大脑区域表达的报道相似。对C57BL/6JLhx9−/−突变小鼠的研究显示，大脑和松果体发育发生了显著变化。具体地说，浅层松果体发育不良，被脑膜和血管组织包围的松果体细胞小簇。深层松果体和松果体柄也缩小了。虽然新生Lhx9−/−突变小鼠的大脑看起来正常，但大约70%的Lhx9−/−小鼠在5-8周龄时出现严重脑积水；这些观察结果首次证明Lhx9基因缺失会导致脑积水，因此表明Lhx9有助于维持正常的脑结构。虽然新生的Lhx9−/−突变小鼠没有脑积水，但这些动物的新生松果体发育不良。因此，Lhx9似乎对哺乳动物松果体的早期发育是必不可少的，而且这种作用不是继发性的。
Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.