Transforming Growth Factor-Beta-Related Signaling in Blastocyst Morphogenesis

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Developmental Biology

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Studies of mouse preimplantation development using embryos cultured in vitro establish the importance of autocrine/paracrine growth regulatory pathways in controlling preimplantation development. Signaling molecules of the Transforming Growth Factor beta (TGF-β) superfamily are potent regulators of development and tissue homeostasis. Smad4 is a central mediator of the TGF-beta-related signaling and is important for numerous processes including cellular growth, differentiation, migration, andextracellular matrix production. Mice lacking Smad4 die around peri-gastrulation period due to defects in epiblast proliferation, mesoderm formation and extraembryonic development. Maternal gene products play key roles in shaping the earliest developmental programs in a wide variety of organisms. Relatively little is known about the functions of mammalian maternal gene products. Maternal Smad4 gene products are abundant in unfertilized eggs as well as cleaving blastomeres of preimplantation mouse embryos. We have conditionally inactivated Smad4 in the female germline. Eggs depleted of maternal Smad4 gene products complete meiosis and are fertilized normally. However, preimplantation development is severely compromised in embryos derived from such eggs even when they are fertilized by wild type sperms, demonstrating the importance of maternally derived Smad4 gene products in early mouse development. The consequences of disrupting maternal TGF-β related signaling on blastocystmorphogenesis, including blastomere cleavage, cell polarity establishment and lineage segregation, will be presented.