Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON M5G 1X8, Canada.
Development. 2013 Jul;140(14):2961-71. doi: 10.1242/dev.094458. Epub 2013 Jun 12.
In mice and humans the X-chromosomal porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands and thus represents a bottleneck for all Wnt signaling. We have generated a mouse line carrying a floxed allele for Porcn and used zygotic, oocyte-specific and visceral endoderm-specific deletions to investigate embryonic and extra-embryonic requirements for Wnt ligand secretion. We show that there is no requirement for Porcn-dependent secretion of Wnt ligands during preimplantation development of the mouse embryo. Porcn-dependent Wnts are first required for the initiation of gastrulation, where Porcn function is required in the epiblast but not the visceral endoderm. Heterozygous female embryos, which are mutant in both trophoblast and visceral endoderm due to imprinted X chromosome inactivation, complete gastrulation but display chorio-allantoic fusion defects similar to Wnt7b mutants. Our studies highlight the importance of Wnt3 and Wnt7b for embryonic and placental development but suggest that endogenous Porcn-dependent Wnt secretion does not play an essential role in either implantation or blastocyst lineage specification.
在小鼠和人类中，X 染色体刺猬同源物（Porcn）基因对于所有 19 种 Wnt 配体的酰化和分泌是必需的，因此代表了所有 Wnt 信号的瓶颈。我们已经生成了携带 Porcn 基因 floxed 等位基因的小鼠品系，并使用合子、卵母细胞特异性和内脏内胚层特异性缺失来研究 Wnt 配体分泌的胚胎和胚胎外要求。我们表明，在小鼠胚胎的着床前发育过程中，不需要 Porcn 依赖性 Wnt 配体的分泌。Porcn 依赖性 Wnt 首先需要启动原肠胚形成，其中 Porcn 功能在外胚层中是必需的，但在内脏内胚层中不是必需的。由于印记 X 染色体失活，杂合雌性胚胎在滋养层和内脏内胚层中都是突变的，完成原肠胚形成，但表现出类似于 Wnt7b 突变体的绒毛膜-尿囊融合缺陷。我们的研究强调了 Wnt3 和 Wnt7b 对胚胎和胎盘发育的重要性，但表明内源性 Porcn 依赖性 Wnt 分泌在植入或胚泡谱系特化中都没有发挥重要作用。
