BMP type II receptor is required for gastrulation and early development of mouse embryos

BMP type II receptor is required for gastrulation and early development of mouse embryos
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DOI:
10.1006/dbio.2000.9670
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发表时间:
2000-05-01
影响因子:
2.7
通讯作者:
Miyazono, K
Miyazono, K
中科院分区:
生物学3区
文献类型:
--
作者:
Beppu, H;Kawabata, M;Miyazono, K

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骨形态发生蛋白(BMP)是转化生长因子β超家族的成员,在小鼠发育过程中发挥着多种作用。BMP II型受体(BMPR-II)是II型丝氨酸/苏氨酸激酶受体,其通过与I型受体的异聚复合物转导BMP的信号,所述I型受体包括激活素受体样激酶2(ALK 2)、ALK 3/BMPR-IA和ALK 6/BMPR-IB。为了阐明BMPR-II在哺乳动物发育中的功能,我们通过基因打靶产生BMPR-II突变小鼠。纯合突变胚胎在卵柱期被捕获,在受精后9.5天不能恢复。组织学分析表明,纯合突变胚胎未能形成有组织的结构,缺乏中胚层。BMPR-II突变体胚胎在形态上与ALK 3/BMPR-IA突变体胚胎非常相似,表明BMPR-II对于小鼠早期发育期间转导BMP信号是重要的。此外,外胚层的BMPR-II突变体胚胎表现出未分化的字符,虽然内脏内胚层的组织特异性基因的表达基本上是正常的。我们的研究结果表明,BMPR-II的功能是必不可少的上胚层分化和中胚层诱导在早期小鼠发育。(C)北京大学出版社.
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta superfamily, play a variety of roles during mouse development. BMP type II receptor (BMPR-II) is a type II serine/threonine kinase receptor, which transduces signals for BMPs through heteromeric complexes with type I receptors, including activin receptor-like kinase 2 (ALK2), ALK3/BMPR-IA, and ALK6/BMPR-IB. To elucidate the function of BIMPR-II in mammalian development, we generated BMPR-II mutant mice by gene targeting. Homozygous mutant embryos were arrested at the egg cylinder stage and could not be recovered at 9.5 days postcoitum. Histological analysis revealed that homozygous mutant embryos failed to form organized structure and lacked mesoderm. The BMPR-II mutant embryos are morphologically very similar to the ALK3/BMPR-IA mutant embryos, suggesting that BMPR-II is important for transducing BMP signals during early mouse development. Moreover, the epiblast of the BMPR-II mutant embryo exhibited an undifferentiated character, although the expression of tissue-specific genes for the visceral endoderm was essentially normal. Our results suggest that the function of BMPR-II is essential for epiblast differentiation and mesoderm induction during early mouse development. (C) 2000 Academic Press.