Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse
Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse
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DOI：
10.1073/pnas.241508898
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Hogan, BLM
中科院分区：
文献类型：
--
作者：
Fujiwara, T;Dunn, NR;Hogan, BLM
有证据表明，哺乳动物胚胎中原始生殖细胞（PGCs）的特化不依赖于母体决定因素。相反，先前对小鼠的遗传分析表明，骨形态发生蛋白4（Bmp4）是PGC和尿囊形成所必需的。Bmp4在滋养层来源的胚外外胚层（ExE）和上胚层来源的胚外中胚层（ExM）中表达，其中PGCs、尿囊原基和成血管细胞。首先被发现。我们已经表明，Bmp4在ExE功能诱导PGCs和尿囊在相邻的上胚层的前体，导致在纯合无效突变体中完全缺乏这两种细胞类型。然而，Bmp4在ExM中的功能完全未知。为了解决这个问题，我们通过将Bmp4缺失的ES细胞与野生型四倍体胚胎聚集来产生四倍体（4N）嵌合体。在这种组合中，野生型四倍体细胞有助于胚外滋养层和原始内胚层谱系，但被排除在外胚层及其衍生物，包括ExM。我们的研究结果清楚地表明，Bmp4在ExM不影响建立无论是PGC或尿囊谱系，但需要PGC的本地化和生存和分化的尿囊。这些发现表明，Bmp4在上胚层来源的组织中表达，通过调节生殖系的发育和胚胎与胎盘之间的血管连接，在生殖中起着至关重要的作用。
Evidence suggests that the specification of primordial germ cells (PGCs) in the mammalian embryo does not depend on maternal determinants. Rather, previous genetic analysis in the mouse has shown that bone morphogenetic protein 4 (Bmp4) is required for the formation of both PGCs and allantois. Bmp4 is expressed in both the trophoblast-derived extraembryonic ectoderm (ExE) and in the epiblast-derived extraembryonic mesoderm (ExM), in which the PGCs, allantois primordium, and angioblasts. are first detected. We have shown that Bmp4 made in the ExE functions to induce precursors of PGCs and allantois in the adjacent epiblast, resulting in complete lack of both cell types in homozygous null mutants. However, the function of Bmp4 in the ExM is totally unknown. To address this question, we generated tetraploid (4N) chimeras by aggregating Bmp4 null ES cells with wild-type tetraploid embryos. In this combination, wild-type tetraploid cells contribute to the extraembryonic trophoblast and primitive endoderm lineages but are excluded from the epiblast and its derivatives, including the ExM. Our results clearly demonstrate that Bmp4 made in the ExM does not affect the establishment of either PGC or allantois lineages, but is required for PGC localization and survival and for the differentiation of the allantois. These findings suggest that Bmp4 expressed in epiblast-derived tissues plays vital roles in reproduction by regulating both the development of the germ line and the vascular connection between the embryo and the placenta.