Horizontal Basal Cell-Specific Deletion of Pax6 Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury.
Horizontal Basal Cell-Specific Deletion of Pax6 Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury.
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DOI：
10.1089/scd.2015.0011
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发表时间：
2015-03
影响因子：
4
通讯作者：
Jun Suzuki;Katsuyasu Sakurai;M. Yamazaki;M. Abe;H. Inada;K. Sakimura;Y. Katori;N. Osumi
中科院分区：
文献类型：
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作者：
Jun Suzuki;Katsuyasu Sakurai;M. Yamazaki;M. Abe;H. Inada;K. Sakimura;Y. Katori;N. Osumi
在哺乳动物的嗅觉上皮（OE）中，嗅觉受体神经元（orn）在动物的一生中不断地再生。OE中的水平基底细胞（hbc）表达上皮标记物角蛋白5 （K5）和干细胞标记物Pax6，被认为是OE中相对静止的组织干细胞。Pax6是中枢神经系统和感觉器官几个发育过程的关键调节因子。尽管Pax6在OE中表达，但其确切作用仍不清楚，特别是在干细胞样乙肝病毒中。为了研究Pax6在OE发育和再生过程中的功能，我们产生了条件Pax6敲除小鼠，携带loxP-floxed Pax6基因。将纯合子pax6敲除小鼠与K5-Cre转基因小鼠杂交，产生hbc特异性pax6敲除（Pax6-cKO）小鼠。我们证实，甲巯咪唑诱导的严重损伤发生3天后，Pax6- cko小鼠的OE 1区中HBCs中Pax6表达的缺失已经充分实现。在这种情况下，OE的再生明显受损；Pax6-cKO小鼠再生OE的OE厚度和orn数量均明显减少。这些结果表明，在严重损伤后的再生过程中，Pax6的表达对于HBCs分化为神经元细胞至关重要。
In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal's lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6 and are considered relatively quiescent tissue stem cells in the OE. Pax6 is a key regulator of several developmental processes in the central nervous system and in sensory organs. Although Pax6 is expressed in the OE, its precise role remains unknown, particularly with respect to stem cell-like HBCs. To investigate the function of Pax6 in the developmental and regenerative processes in the OE, we generated conditional Pax6-knockout mice carrying a loxP-floxed Pax6 gene. Homozygous Pax6-floxed mice were crossed with K5-Cre transgenic mice to generate HBC-specific Pax6-knockout (Pax6-cKO) mice. We confirmed that the deletion of Pax6 expression in HBCs was sufficiently achieved in zone 1 of the OE in Pax6-cKO mice 3 days after methimazole-induced severe damage. In this condition, regeneration of the OE was dramatically impaired; both OE thickness and the number of ORNs were significantly decreased in the regenerated OE of Pax6-cKO mice. These results suggest that Pax6 expression is essential for HBCs to differentiate into neuronal cells during the regeneration process following severe injury.