Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis
Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis
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DOI：
10.1101/gad.9.24.3027
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发表时间：
1995-12-15
影响因子：
10.5
通讯作者：
Behringer, RR
中科院分区：
文献类型：
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作者：
Mishina, Y;Suzuki, A;Behringer, RR
骨形态发生蛋白（BMPs）是一种与细胞表面受体相互作用的分泌性蛋白质，在脊椎动物胚胎发育过程中发挥着重要作用。Bmpr，也称为ALK-3和Brk-1，编码BMP-2和BMP-4的I型转化生长因子-β（TGF-β）家族受体。Bmpr在小鼠早期胚胎发育和大多数成年小鼠组织中广泛表达。为了研究Bmpr在哺乳动物发育过程中的功能，我们产生了Bmpr突变小鼠。胚胎9.5天（E9.5）后，没有纯合子突变体从杂合子交配恢复。具有形态缺陷的纯合突变体在E7.0时首次检测到，并且比正常的小。形态学和分子生物学检测表明，突变体胚中没有形成中胚层。在体外培养的纯合子突变体囊胚的生长特性是无法区分的控制，但是，胚胎外胚层（外胚层）细胞增殖减少在所有纯合子突变体在E6.5之前，形态异常已成为突出。E7.0突变胚胎产生的畸胎瘤含有来自所有三个胚层的衍生物，但比对照组更小，产生的中胚层细胞类型更少，如肌肉和软骨。这些结果表明，通过这种I型BMP-2/4受体的信号是不必要的植入前或初始植入后的发展，但可能是必不可少的诱导事件，导致原肠胚形成过程中中胚层的形成，后来的中胚层细胞类型的一个子集的分化。
Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell-surface receptors and are believed to play a variety of important roles during vertebrate embryogenesis. Bmpr, also known as ALK-3 and Brk-1, encodes a type I transforming growth factor-beta (TGF-beta) family receptor for BMP-2 and BMP-4. Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult mouse tissues. To study the function of Bmpr during mammalian development, we generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutants were recovered from heterozygote matings. Homozygous mutants with morphological defects were first detected at E7.0 and were smaller than normal. Morphological and molecular examination demonstrated that no mesoderm had formed in the mutant embryos. The growth characteristics of homozygous mutant blastocysts cultured in vitro were indistinguishable from those of controls; however, embryonic ectoderm (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5 before morphological abnormalities had become prominent. Teratomas arising from E7.0 mutant embryos contained derivatives from all three germ layers but were smaller and gave rise to fewer mesodermal cell types, such as muscle and cartilage, than controls. These results suggest that signaling through this type I BMP-2/4 receptor is not necessary for preimplantation or for initial postimplantation development but may be essential for the inductive events that lead to the formation of mesoderm during gastrulation and later for the differentiation of a subset of mesodermal cell types.