Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development
Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development
复制标题
DOI：
10.1242/dev.103226
复制
发表时间：
2014-01-01
期刊：
影响因子：
4.6
通讯作者：
Flamant, Frederic
中科院分区：
文献类型：
--
作者：
Fauquier, Teddy;Chatonnet, Fabrice;Flamant, Frederic
甲状腺激素是中枢神经系统正常发育所必需的，如影响甲状腺功能减退患者的活性甲状腺激素水平低的严重智力迟钝综合征所示。在甲状腺功能减退小鼠小脑中观察到的出生后缺陷在Thra（编码普遍存在的TR α 1受体的基因）显性负突变杂合子小鼠中重现。使用CRE/loxP介导的条件表达方法，我们发现，这种突变主要改变浦肯野细胞和Bergmann胶质细胞，两种小脑特异性细胞类型的分化。这些原发性缺陷间接影响小脑的发育。值得注意的是，颗粒细胞前体的向内迁移和终末分化受损。因此，尽管其受体分布广泛，甲状腺激素靶向少数细胞类型，发挥主导作用的网络中的细胞相互作用，管理正常小脑成熟。
Thyroid hormone is necessary for normal development of the central nervous system, as shown by the severe mental retardation syndrome affecting hypothyroid patients with low levels of active thyroid hormone. The postnatal defects observed in hypothyroid mouse cerebellum are recapitulated in mice heterozygous for a dominant-negative mutation of Thra, the gene encoding the ubiquitous TR alpha 1 receptor. Using CRE/loxP-mediated conditional expression approach, we found that this mutation primarily alters the differentiation of Purkinje cells and Bergmann glia, two cerebellum-specific cell types. These primary defects indirectly affect cerebellum development in a global manner. Notably, the inward migration and terminal differentiation of granule cell precursors is impaired. Therefore, despite the broad distribution of its receptors, thyroid hormone targets few cell types that exert a predominant role in the network of cellular interactions that govern normal cerebellum maturation.