One of the earliest events in mammalian embryogenesis is the formation of the inner cell mass (ICM) and the subse- quent delamination of primitive endoderm. We have found that mRNA for ﬁbroblast growth factor (FGF)-4, but not FGF-3, is expressed in preimplantation mouse blastocysts and that the FGF-4 polypeptide is present in ICM cells. ICM-like embryonal carcinoma cells and embryonic stem cells also express FGF-4. Conversely, differentiated embryonal carcinoma cells in the endoderm lineage express FGF-3, but not FGF-4 mRNA. Although mouse embryos expressed FGF-4 mRNA from the 1-cell stage, embryos cultured from the 2-cell through the blastocyst stage in the presence of recombinant FGF-4 did not respond mitogenically. However, when ICMs that were isolated by immunosurgery were cultured with FGF- 4, the number of morphologically distinct, differentiated parietal endoderm cells growing out onto the coverslip increased, without an increase in the number of undiffer- entiated ICM cells. ICM outgrowths cultured with FGF-4 increased their secretion of 92×103 Mrgelatinase and tissue plasminogen activator, a hallmark of migrating cells. Receptors for FGF-4 (FGFR-3 and FGFR-4) are expressed in all cells of the mouse blastocyst. These ﬁndings indicate that FGF-4 produced by undifferentiated ICM cells acts in the peri-implantation period of embryogenesis to inﬂuence the production and behavior of endoderm cells derived from them. Key words: ﬁbroblast growth factor, mouse embryogenesis, metallo
Obstetrics and Gynecology
Rappolee D. A., Basilico, C., Patel, Y., and Werb, Z. 1994. Expression and function of FGF-4 in peri-implantation development in mouse embryos. Development. 120, 2259-2269.