Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands

Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands
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DOI:
10.1006/dbio.1997.8827
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发表时间:
1998-03-01
影响因子:
2.7
通讯作者:
Capecchi, MR
Capecchi, MR
中科院分区:
生物学3区
文献类型:
--
作者:
Manley, NR;Capecchi, MR

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脊椎动物的胸腺、甲状腺和甲状旁腺由咽区发育而来,其中咽内胚层和咽弓的神经嵴细胞都有贡献。Hoxa3突变的纯合子在这三个器官的发育中都有缺陷。Hoxa3相似基因Hoxb3和Hoxd3的作用通过检测各种突变组合进行了研究。在Hoxa3单突变体中所见的甲状腺缺陷在其任何一种类似物的双突变体中都加重了,尽管双突变体组合都不会导致甲状腺发育不全。结果表明,这些基因在甲状腺发育中的主要作用是它们对鳃末梢小体的发育和迁移的影响,而鳃末梢小体为甲状腺提供了滤泡旁细胞或c细胞。Hoxb3、Hoxd3双突变体在胸腺和甲状旁腺中无明显缺陷。然而,从Hoxb3、Hoxd3双突变体(Hoxa3(+/-)、Hoxb3(-/-)、Hoxd3(-/-))中去除Hoxa3的一个功能拷贝会导致胸腺和甲状旁腺无法迁移到喉咙的正常位置。在发育过程中,调节组织运动的分子机制所知甚少。这些结果表明,Hoxa3、Hoxb3和Hoxd3在介导咽器官原基迁移中具有高度重叠的功能。此外,Hoxa3在胸腺、甲状旁腺和甲状腺发育中具有独特的功能,这种独特的功能可能是由Hoxa3的表达赋予的,而不是Hoxb3和Hoxd3在咽袋内胚层中的表达。(C) 1998学术出版社。
The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal region, with contributions both from pharyngeal endoderm and from neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have defects in the development of all three organs. Roles for the Hoxa3 paralogs, Hoxb3 and Hoxd3, were investigated by examining various mutant combinations. The thyroid defects seen in Hoxa3 single mutants are exacerbated in double mutants with either of its paralogs, although none of the double-mutant combinations resulted in thyroid agenesis. The results indicate that the primary role of these genes in thyroid development is their effect on the development and migration of the ultimobranchial bodies, which contribute the parafollicular or C-cells to the thyroid. Hoxb3,Hoxd3 double mutants show no obvious defects in the thymus or parathyroids. However, the removal of one functional copy of Hoxa3 from the Hoxb3,Hoxd3 double mutants (Hoxa3(+/-),Hoxb3(-/-),Hoxd3(-/-)) results in the failure of the thymus and parathyroid glands to migrate to their normal positions in the throat. Very little is known about the molecular mechanisms used to mediate the movement of tissues during development. These results indicate that Hoxa3, Hoxb3, and Hoxd3 have highly overlapping functions in mediating the migration of pharyngeal organ primordia. In addition, Hoxa3 has a unique function with respect to its paralogs in thymus, parathyroid, and thyroid development, This unique function may be conferred by the expression of Hoxa3, but not Hoxb3 nor Hoxd3, in the pharyngeal pouch endoderm. (C) 1998 Academic Press.