title: GDF3 at the crossroads of TGF-beta signaling.
abstract: Embryonic stem (ES) cells present an excellent system for addressing the relevance of our current knowledge about how cell fate is determined and how cells integrate multiple signals into a single outcome as a function of time. Many of the factors that mediate these phenomena have been discovered through classical embryological experiments and are organized into several major signal transduction pathways including TGF-beta/BMP, Jak-STAT, Hedgehog, Wnt, Notch and FGF/MAPK. This review will summarize the current understanding of TGF-beta signaling in ES and focus on early embryological roles of the TGF-beta member, GDF-3. GDF-3 is associated with the undifferentiated state of ES cells and two recent and contradictory reports examined the function and mechanism of GDF-3 in the context of both stem cells and early embryonic differentiations. While Levine and Brivanlou found that GDF-3 inhibits its own subfamily members (the BMPs), Chen and colleagues found that GDF-3 acts as a nodal-like TGF-beta ligand. These combined findings raise the intriguing possibility that GDF-3 acts as a bi-functional protein, to regulate the balance between the two modes of TGF-beta signaling.
authors.affiliation: Laboratory of Molecular Vertebrate Embryology, Rockefeller University, New York, New York 10021, USA. levinea@mail.rockefeller.edu
authors.forename: Ariel J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055451:Growth Differentiation Factor 3; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525974:GDF3 protein, human; D055451:Growth Differentiation Factor 3; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta