The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse
The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse
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DOI：
10.1177/002215540405200508
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发表时间：
2004-05-01
影响因子：
3.2
通讯作者：
Chisaka, O
中科院分区：
文献类型：
--
作者：
Kameda, Y;Arai, Y;Chisaka, O
Hoxa3基因定向缺失的小鼠有第三鳃弓和眼袋的衍生品缺陷。为了探讨Hoxa3基因在甲状旁腺器官发生中的作用，我们使用分泌蛋白(SP)-1/嗜铬粒蛋白A抗血清，通过免疫组织化学(IHC)检测了第三个咽囊的发育，该抗血清识别甲状旁腺的最初形成。胚胎11.5天，野生型胚胎第三咽囊颅区出现SP-1/Chromoranin A免疫反应阳性的甲状旁腺初级雏形。在Hoxa3缺失突变体中，第三个咽囊正常形成，但未能分化为甲状旁腺雏形，没有显示SP-1/嗜铬粒蛋白A的免疫反应。使用鸡-鹌鹑嵌合体的经典研究表明，外胚间充质神经脊细胞对于咽囊起源的器官，包括胸腺和甲状旁腺的正常发育是必需的。为了观察Hoxa3突变体中间充质神经脊细胞的迁移和发育，将杂合子与连接蛋白43-LacZ转基因小鼠杂交，在转基因小鼠中，β-半乳糖苷酶的表达是神经脊细胞特有的。在Hoxa3纯合子和野生型中，外胚间充质神经脊细胞密集分布在包括第三咽弓在内的咽弓周围，并包围着第三袋上皮。这些结果表明，Hoxa3基因的缺失影响了第三咽囊形成甲状旁腺雏形的固有能力，而对神经脊细胞的迁移没有明显的影响。
Mice with a targeted deletion of the Hoxa3 gene have defects of derivatives of the third branchial arch and pouch. To address the role of the Hoxa3 gene in parathyroid organogenesis, we examined the third pharyngeal pouch development by immunohistochemistry (IHC) using the secretory protein (SP)-1/chromogranin A antiserum, which recognizes the parathyroid from its initial formation onward. At embryonic day (E) 11.5, the SP-1/chromogranin A-immunoreactive primary rudiment of the parathyroid appeared in the cranial region of the third pharyngeal pouch of wild-type embryos. In Hoxa3-null mutants, the third pharyngeal pouch was normally formed but failed to differentiate into the parathyroid rudiment, showing no immunoreactivity for SP-1/chromogranin A. Classic studies using chick-quail chimeras have demonstrated that the ectomesenchymal neural crest cells are required for proper development of the pharyngeal pouch-derived organs, including the thymus and parathyroid glands. To visualize the migration and development of mesenchymal neural crest cells in Hoxa3 mutants, the heterozygotes were crossed with connexin43-lacZ transgenic mice in which beta-galactosidase expression was specific to the neural crest cells. In Hoxa3 homozygotes and in wild types, ectomesenchymal neural crest cells densely populated the pharyngeal arches, including the third one, and surrounded the third pouch epithelium. These results indicate that lack of the Hoxa3 gene affects the intrinsic ability of the third pharyngeal pouch to form the parathyroid rudiment and has no detectable effect on the migration of neural crest cells.