Rax regulates hypothalamic tanycyte differentiation and barrier function in mice.

Rax regulates hypothalamic tanycyte differentiation and barrier function in mice.
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DOI:
10.1002/cne.23451
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发表时间:
2014-03
影响因子:
2.5
通讯作者:
Blackshaw, Seth
Blackshaw, Seth
中科院分区:
医学3区
文献类型:
--
作者:
Miranda-Angulo, Ana L.;Byerly, Mardi S.;Mesa, Janny;Wang, Hong;Blackshaw, Seth

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腹侧第三脑室壁由两个不同的细胞群组成:单细胞和室管膜细胞。 Tanycytes 调节下丘脑生理学的许多方面,但人们对调节其发育和功能的转录网络知之甚少。我们观察到视网膜和前神经皱襞同源框转录因子(Rax)在下丘脑单胞细胞中选择性表达,并显示出与下丘脑室管膜细胞标记物(例如 Rarres2(视黄酸受体应答器))互补的表达模式。为了确定 Rax 是否控制单胞分化和功能,我们生成了 Rax 单倍体不足的小鼠,并检查了它们成年后的细胞和分子表型。这些小鼠看起来非常正常,但仔细检查发现第三心室壁变薄,单细胞和室管膜标记物减少。这些实验表明 Rax 是下丘脑单细胞和室管膜细胞分化所必需的。 Rax 单倍体不足还导致 α2 单胞区异位存在室管膜细胞,该区域通常很少发现室管膜细胞,这表明 Rax 是 α2 单胞分化选择性需要的。心室壁的这些变化与伊文思蓝示踪剂从心室到下丘脑实质的扩散减少有关,对这些小鼠的总体解剖或行为表型没有明显影响。总之,我们提供的证据表明 Rax 是下丘脑单细胞和室管膜细胞的正常分化和模式以及维持脑脊液-下丘脑屏障所必需的。
The wall of the ventral third ventricle is composed of two distinct cell populations: tanycytes and ependymal cells. Tanycytes regulate many aspects of hypothalamic physiology, but little is known about the transcriptional network that regulates their development and function. We observed that the retina and anterior neural fold homeobox transcription factor (Rax) is selectively expressed in hypothalamic tanycytes, and showed a complementary pattern of expression to markers of hypothalamic ependymal cells, such as Rarres2 (retinoic acid receptor responder). To determine whether Rax controls tanycyte differentiation and function, we generated Rax haploinsufficient mice and examined their cellular and molecular phenotype in adulthood. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of both tanycyte and ependymal markers. These experiments show that Rax is required for hypothalamic tanycyte and ependymal cell differentiation. Rax haploinsufficiency also resulted in the ectopic presence of ependymal cells in the α2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma, with no apparent repercussion on the gross anatomical or behavioral phenotype of these mice. In conclusion, we have provided evidence that Rax is required for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells, as well as for maintenance of the cerebrospinal fluid-hypothalamus barrier.
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发表时间: 1986-03
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