GDF3

GDF3, or Growth Differentiation Factor 3, is a secreted signaling protein in the transforming growth factor beta (TGF-β) superfamily. It is related to other growth factors such as GDF1 and participates in regulating embryonic development and cellular differentiation across vertebrates. In some species the protein is also referred to as Vg-related gene 2 (Vgr-2).

In mammals, GDF3 is expressed during early embryogenesis and in pluripotent cells, including embryonic stem cells. It has been implicated in maintaining pluripotency and guiding lineage decisions during gastrulation. GDF3 can antagonize BMP signaling, a context that promotes neural induction, while in other contexts it can activate SMAD2/3 signaling via Activin/Nodal-type receptors, supporting endoderm and mesoderm formation. These dual actions reflect its role as a context-dependent modulator of TGF-β pathways.

GDF3 signals through type I and II serine/threonine kinase receptors to activate intracellular SMAD transcription factors, with the downstream response depending on the cellular milieu. By shaping BMP and Nodal-like signaling, GDF3 influences cell fate decisions, tissue patterning, and developmental timing in embryos and stem cell cultures.

Research on GDF3 covers developmental biology, stem cell research, and disease. Altered GDF3 expression has been reported in certain cancers and other conditions, making it a focus of studies on tumor biology and regenerative medicine. Understanding GDF3 signaling contributes to broader insights into TGF-β family functions in development and stem cell regulation.