The yolk sac of the Pdgfraph/Pdgfraph embryo with a C57BL/6 genetic background was reported to be hypertrophic as compared with the wild-type embryo, suggesting a role of PDGFRot in the early process of yolk sac formation. However, Pdgfraph/Pdgfraph mutants with other genetic backgrounds, such as our outbred lines, continued to develop even to the perinatal stage, maintaining nearly normal parietal and visceral yolk sac formation. Therefore, the functional role of PDGFRa in the development of the parietal and visceral yolk sac may be compromised in these mutants. However, we found here that the IPY is entirely absent in these Pdgfraph/Pdgfraph mutants, indicating an absolute requirement of PDGFRa for IPY development. ventolin inhalers
How then does PDGFRa regulate the development of the IPY? It is likely that the IPY is an extension of the preformed endodermal layer rather than being newly differentiated epithelium. The IPY, therefore, develops through proliferation and invagination of pre-existing endodermal epithelial cells, in which PDGFRa plays an essential role. If the columnar and squamous epithelia of the IPY are derived from visceral and parietal endoderm, respectively, its invagination may occur from both sides of the periplacental and villous visceral endoderm. It is of note that strong calbindin-D9k expression was found at the inner margin of the periplacental endoderm of the Pdgfraph/ Pdgfraph placenta (Fig. 4, D and H) and that the calbindin-D9k-positive cells formed villous structures (Fig. 4H). Indeed, columnar epithelium of normal IPY formed villous structures at the beginning of invagination (Fig. 1, С and E, Fig. 4E).