GDF3 explained

Growth differentiation factor-3 (GDF3), also known as Vg-related gene 2 (Vgr-2) is protein that in humans is encoded by the GDF3 gene.^[1] GDF3 belongs to the transforming growth factor beta (TGF-β) superfamily. It has high similarity to other TGF-β superfamily members including Vg1 (found in frogs) and GDF1.^[1]

Tissue distribution

Expression of GDF3 occurs in ossifying bone during embryonic development and in the brain, thymus, spleen, bone marrow and adipose tissue of adults.^{[2] [3]}

Function

GDF3 is a bi-functional protein that has some intrinsic activity and also modulate other TGF-β superfamily members, e.g. potentiates the activity of NODAL. It may also inhibit other TGF-β superfamily members (i.e. BMPs), thus regulating the balance between different modes of TGF-beta signaling.^[4] It has been shown to negatively and positively control differentiation of embryonic stem cells in mice and humans.^[5] This molecule plays a role in mesoderm and definitive endoderm formation during the pre-gastrulation stages of development.^[2]

Further reading

• Davila S, Froeling FE, Tan A . New genetic associations detected in a host response study to hepatitis B vaccine. . Genes Immun. . 11 . 3 . 232–8 . 2010 . 20237496 . 10.1038/gene.2010.1 . 11183658 . etal.
• McPherron AC, Lee SJ . GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. . J. Biol. Chem. . 268 . 5 . 3444–9 . 1993 . 10.1016/S0021-9258(18)53714-5 . 8429021 . free .
• Levine AJ, Brivanlou AH . GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos. . Development . 133 . 2 . 209–16 . 2006 . 16339188 . 10.1242/dev.02192 . 35923560 .
• Ye M, Berry-Wynne KM, Asai-Coakwell M . Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. . Hum. Mol. Genet. . 19 . 2 . 287–98 . 2010 . 19864492 . 10.1093/hmg/ddp496 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Ducy P, Karsenty G . The family of bone morphogenetic proteins. . Kidney Int. . 57 . 6 . 2207–14 . 2000 . 10844590 . 10.1046/j.1523-1755.2000.00081.x . free .
• Gopalan A, Dhall D, Olgac S . Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. . Mod. Pathol. . 22 . 8 . 1066–74 . 2009 . 19396148 . 10.1038/modpathol.2009.66 . etal. free .
• Clark HF, Gurney AL, Abaya E . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Andersson O, Korach-Andre M, Reissmann E . Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity. . Proc. Natl. Acad. Sci. U.S.A. . 105 . 20 . 7252–6 . 2008 . 18480259 . 10.1073/pnas.0800272105 . 2438236 . 2008PNAS..105.7252A . etal. free .
• Levine AJ, Levine ZJ, Brivanlou AH . GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high doses. . Dev. Biol. . 325 . 1 . 43–8 . 2009 . 18823971 . 3740937 . 10.1016/j.ydbio.2008.09.006 .

Notes and References

1. Caricasole AA, van Schaik RH, Zeinstra LM, Wierikx CD, van Gurp RJ, van den Pol M, Looijenga LH, Oosterhuis JW, Pera MF, Ward A, de Bruijn D, Kramer P, de Jong FH, van den Eijnden-van Raaij AJ . Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours . Oncogene . 16 . 1 . 95–103 . January 1998 . 9467948 . 10.1038/sj.onc.1201515 . free .
2. Chen C, Ware SM, Sato A, Houston-Hawkins DE, Habas R, Matzuk MM, Shen MM, Brown CW . The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo . Development . 133 . 2 . 319–29 . January 2006 . 16368929 . 10.1242/dev.02210 . 14505029 .
3. Hexige S, Guo J, Ma L, Sun Y, Liu X, Ma L, Yan X, Li Z, Yu L . Expression pattern of growth/differentiation factor 3 in human and murine cerebral cortex, hippocampus as well as cerebellum . Neurosci. Lett. . 389 . 2 . 83–7 . December 2005 . 16126341 . 10.1016/j.neulet.2005.06.071 . 25293256 .
4. 10.4161/cc.5.10.2771 . Levine A, Brivanlou A . GDF3 at the crossroads of TGF-beta signaling . Cell Cycle . 5 . 10 . 1069–73 . 2006 . 16721050. free .
5. Levine A, Brivanlou A . GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos . Development . 133 . 2 . 209–16 . 2006 . 16339188 . 10.1242/dev.02192. 35923560 .