Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice
Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice
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DOI：
10.1007/s00441-004-1042-z
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Kameda, Y
中科院分区：
文献类型：
--
作者：
Chisaka, O;Kameda, Y
Hoxa3基因突变导致双侧颈总动脉缺陷，颈总动脉起源于第三鳃弓动脉。起源于弓动脉的大动脉中膜由外胚间充质神经脊细胞形成。为了研究第三弓动脉退行性变的病因，我们产生了Hoxa3纯合子零突变胚胎，该胚胎在神经脊细胞中表达由连接蛋白43(Cx43)：启动子驱动的LacZ标记转基因。用全贴壁X-半乳糖苷酶染色和免疫组织化学方法检测β-半乳糖苷酶在小鼠胚胎中的表达。在Hoxa3纯合子中，神经脊细胞从神经管向第三鳃弓的迁移没有受到影响。第三弓动脉的初始形成也未受到干扰。然而，在胚胎11.5天(E11.5)，当第三咽弓开始分化时，动脉开始退化。E12.5缺失突变体的颈内动脉和颈外动脉起源于背主动脉，表现为颈动脉管的异常持续性。野生型小鼠的第三个咽弓与第四个和第二个咽弓在E12.0融合。然而，在Hoxa3缺失突变体中，融合被推迟，并且在E12.5仍然可以辨认出发育不良的第三咽弓。此外，与野生型相比，缺失型突变体第三弓的增殖细胞数量较少。因此，Hoxa3是第三咽弓生长和分化所必需的。第三咽弓发育不良可导致颈动脉系统异常。
Genetic disruption of Hoxa3 results in bilateral defects of the common carotid artery, which is derived from the third branchial arch artery. The tunica media of the great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells. The expression of beta-galactosidase in these mouse embryos was examined by both whole-mount X-gal staining and immunohistochemistry with the monoclonal P-galactosidase antibody on sections. The migration of neural crest cells from the neural tube to the third branchial arch was not affected in the Hoxa3 homozygotes. The initial formation of the third arch artery was also not disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when differentiation of the third pharyngeal arch began. The internal and external carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed an abnormal persistence of the ductus caroticus. The third pharyngeal arch of wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3 null mutants, however, the fusion was delayed, and the hypoplastic third pharyngeal arch was still discerned at E12.5. Moreover, the number of proliferating cells in the third arch of the null mutants was small compared with that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation of the third pharyngeal arch. The defective development of the third pharyngeal arch may induce the anomalies of the carotid artery system.