Involvement of thyroid hormones in chicken embryonic brain development
Involvement of thyroid hormones in chicken embryonic brain development
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DOI：
10.1016/j.ygcen.2008.11.014
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发表时间：
2009-08-01
影响因子：
2.7
通讯作者：
Reyns, Geert E.
中科院分区：
文献类型：
--
作者：
Darras, Veerle M.;Van Herck, Stijn L. J.;Reyns, Geert E.
甲状腺激素通过刺激和协调细胞的增殖、迁移和分化，在脊椎动物脑发育中起着重要作用。已经确定了参与这些过程的几个促甲状腺激素应答基因，但这些信息主要来自大脑发育晚期的研究，而对胚胎促甲状腺激素分泌开始之前的更早期阶段知之甚少。我们选择鸡胚胎来研究三萜类化合物在早期和晚期大脑发育中的作用。在测试的最初阶段（第4天），鸡的大脑中就发现了T-4和T-3。在调节其生物利用度和作用的蛋白质的个体发育表达谱中，包括TH转运蛋白、脱碘酶和TH受体，发现了T-3参与脑发育的间接线索。所有这些基因都在孵化第2天测试的全胚胎中表达，并在第4天之后测试的发育中的大脑中表达。它们的分布模式随着时间的推移以及所研究的大脑区域和细胞类型而变化。在孵育后期引起的甲状腺功能减退会干扰小脑的细胞迁移，这为大脑发育后期对三手环的需求提供了更直接的证据。目前还没有直接的形态学证据来证明在孵育的前半期需要th，但是对端脑的微阵列分析显示，在甲状腺功能减退的胚胎中，基因表达谱明显不同。在体外培养的鸡胚中，体内敲除TH转运体和脱碘酶为更详细地研究TH在早期大脑发育中的作用提供了一个很好的工具。(C) 2008爱思唯尔公司版权所有。
Thyroid hormones (THs) play an important role in vertebrate brain development by stimulating and coordinating cell proliferation, migration and differentiation. Several TH-responsive genes involved in these processes have been identified, but the information is mainly derived from studies of late brain development, while relatively little is known about the more early stages, prior to the onset of embryonic TH secretion. We have chosen the chick embryo to investigate the role of THs in both late and early brain development. T-4 and T-3 are found in chicken brain from the earliest stages tested (day 4). Indirect clues for the involvement of T-3 in brain development are found in the ontogenetic expression profiles of proteins regulating its bioavailability and action, including TH transporters, deiodinases and TH-receptors. All of them are expressed in whole embryos tested on day 2 of incubation and in developing brain tested from day 4 onwards. Their distribution patterns vary over time and according to the brain area and cell type studied. Hypothyroidism induced during the second half of incubation disturbs cell migration in the cerebellum, providing more direct evidence for the requirement for THs during the laterstages of brain development. Direct morphological proof for the requirement for THs during the first half of incubation is still missing, but microarray analysis of telencephalon shows a clearly divergent gene expression profile in hypothyroid embryos. In vivo knockdown of TH transporters and deiodinases in chick embryos cultured ex ovo provides an excellent tool to study the role of THs in early brain development in more detail. (C) 2008 Elsevier Inc. All rights reserved.