Pesce Maurizio, Klinger Francesca Gioia, De Felici Massimo
Department of Public Health and Cell Biology, Section of Histology and Embryology, University of Rome Tor Vergata, Rome, Italy.
Mech Dev. 2002 Mar;112(1-2):15-24. doi: 10.1016/s0925-4773(01)00624-4.
Primordial germ cells (PGCs) are the embryonic precursors of the gametes of the adult. PGCs derive from cells of the most proximal part of the cup-shaped epiblast corresponding to the presumptive region of the extraembryonic mesoderm. At 7.2 days post coitum (dpc) a small group of PGCs located at the base of the allantois can be recognised due to a strong alkaline phosphatase activity. Thus far, scant information was available on the mechanism(s) controlling the lineage of PGCs in the mouse embryo. However, results obtained in mice defective for bone morphogenetic protein-4 (Bmp4) secreted molecule revealed that this growth factor has important functions for the derivation of PGCs from extraembryonic mesoderm cells. In this paper, we have studied the effects in culture of Bmp4 on epiblast cells obtained from egg-cylinder stage mouse embryos (5.5-6.0 dpc) and PGCs from 11.5 dpc embryos. We found that Bmp4 treatment enables recruitment of pluripotent cells to a PGC phenotype by a multi-step process involving an initial pre-commitment of epiblast cells and a following stage of PGC phenotypic determination. We further provide evidences that Bmp4 may promote the growth of gonadal PGCs through a Smad1/4 signalling.
原始生殖细胞（PGCs）是成年个体配子的胚胎前体。PGCs来源于杯状上胚层最近端的细胞，对应于胚外中胚层的预定区域。在交配后7.2天（dpc），由于强碱性磷酸酶活性，可以识别位于尿囊基部的一小群PGCs。到目前为止，关于控制小鼠胚胎中PGCs谱系的机制的信息很少。然而，在骨形态发生蛋白-4（Bmp4）分泌分子缺陷的小鼠中获得的结果表明，这种生长因子对于从胚外中胚层细胞衍生PGCs具有重要功能。在本文中，我们研究了Bmp4在培养中对从卵柱期小鼠胚胎（5.5 - 6.0 dpc）获得的上胚层细胞和11.5 dpc胚胎的PGCs的影响。我们发现，Bmp4处理通过一个多步骤过程使多能细胞募集到PGC表型，该过程涉及上胚层细胞的初始预决定和随后的PGC表型确定阶段。我们进一步提供证据表明，Bmp4可能通过Smad1/4信号促进性腺PGCs的生长。
