Growth differentiation factor explained

Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development.^[1]

Types

Several members of this subfamily have been described, and named GDF1 through GDF15.

• GDF1 is expressed chiefly in the nervous system and functions in left-right patterning and mesoderm induction during embryonic development.^[2]
• GDF2 (also known as BMP9) induces and maintains the response embryonic basal forebrain cholinergic neurons (BFCN) have to a neurotransmitter called acetylcholine, and regulates iron metabolism by increasing levels of a protein called hepcidin.^{[3] [4]}
• GDF3 is also known as "Vg-related gene 2" (Vgr-2). Expression of GDF3 occurs in ossifying bone during embryonic development and in the thymus, spleen, bone marrow brain, and adipose tissue of adults. It has a dual nature of function; it both inhibits and induces early stages of development in embryos.^{[5] [6] [7]}
• GDF5 is expressed in the developing central nervous system, with roles in the development of joints and the skeleton, and increasing the survival of neurones that respond to a neurotransmitter called dopamine.^{[8] [9] [10]}
• GDF6 interacts with bone morphogenetic proteins to regulate ectoderm patterning, and controls eye development.^{[11] [12] [13]}
• GDF8 is now officially known as myostatin and controls the growth of muscle tissue.^[14]
• GDF9, like GDF3, lacks one cysteine relative to other members of the TGF-β superfamily. Its gene expression is limited to the ovaries, and it has a role in ovulation.^{[15] [16]}
• GDF10 is closely related to BMP3 and has a roles in head formation and, it is presumed, in skeletal morphogenesis.^{[17] [18]} It is also known as BMP-3b.
• GDF11 controls anterior-posterior patterning by regulating the expression of Hox genes,^[19] and regulates the number of olfactory receptor neurons occurring in the olfactory epithelium,^[20] and numbers of retinal ganglionic cells developing in the retina.^[21]
• GDF15 (also known as TGF-PL, MIC-1, PDF, PLAB, and PTGFB) has a role in regulating inflammatory and apoptotic pathways during tissue injury and certain disease processes.^{[22] [23] [24]}

Notes and References

1. Herpin A, Lelong C, Favrel P . Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans . Dev Comp Immunol . 28 . 5 . 461–85 . 2004 . 15062644 . 10.1016/j.dci.2003.09.007.
2. Rankin C, Bunton T, Lawler A, Lee S . Regulation of left-right patterning in mice by growth/differentiation factor-1 . Nat Genet . 24 . 3 . 262–5 . 2000 . 10700179 . 10.1038/73472. 6787053 .
3. Lopez-Coviella I, Follettie M, Mellott T, Kovacheva V, Slack B, Diesl V, Berse B, Thies R, Blusztajn J . Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons . Proc Natl Acad Sci USA . 102 . 19 . 6984–9 . 2005 . 15870197 . 10.1073/pnas.0502097102 . 1088172. 2005PNAS..102.6984L . free .
4. Truksa J, Peng H, Lee P, Beutler E . Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6 . Proc Natl Acad Sci USA . 103 . 27 . 10289–93 . 2006 . 16801541 . 10.1073/pnas.0603124103 . 1502450. 2006PNAS..10310289T . free .
5. Levine A, Brivanlou A . GDF3 at the crossroads of TGF-beta signaling . Cell Cycle . 5 . 10 . 1069–73 . 2006 . 16721050 . 10.4161/cc.5.10.2771. free .
6. 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.
7. Chen C, Ware S, Sato A, Houston-Hawkins D, Habas R, Matzuk M, Shen M, Brown C . The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo . Development . 133 . 2 . 319–29 . 2006 . 16368929 . 10.1242/dev.02210.
8. O'Keeffe G, Dockery P, Sullivan A . Effects of growth/differentiation factor 5 on the survival and morphology of embryonic rat midbrain dopaminergic neurones in vitro . J Neurocytol . 33 . 5 . 479–88 . 2004 . 15906156 . 10.1007/s11068-004-0511-y. 25940876 .
9. Buxton P, Edwards C, Archer C, Francis-West P . Growth/differentiation factor-5 (GDF-5) and skeletal development . J Bone Joint Surg Am . 83-A Suppl 1 . Pt 1 . S23–30 . 2001 . 11263662.
10. Francis-West P, Parish J, Lee K, Archer C . BMP/GDF-signalling interactions during synovial joint development . Cell Tissue Res . 296 . 1 . 111–9 . 1999 . 10199971 . 10.1007/s004410051272. 21942870 .
11. Chang C, Hemmati-Brivanlou A . Xenopus GDF6, a new antagonist of noggin and a partner of BMPs . Development . 126 . 15 . 3347–57 . 1999 . 10.1242/dev.126.15.3347 . 10393114.
12. Asai-Coakwell M, French C, Berry K, Ye M, Koss R, Somerville M, Mueller R, van Heyningen V, Waskiewicz A, Lehmann O . GDF6, a novel locus for a spectrum of ocular developmental anomalies . American Journal of Human Genetics . 80 . 2 . 306–15 . 2007 . 17236135 . 10.1086/511280 . 1785352.
13. Hanel M, Hensey C . Eye and neural defects associated with loss of GDF6 . BMC Dev Biol . 6. 43 . 2006. 17010201 . 10.1186/1471-213X-6-43 . 1609107 . free .
14. 9139826 . 10.1038/387083a0 . 387 . 6628 . Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member . May 1997 . Nature . 83–90 . McPherron AC, Lawler AM, Lee SJ . 4271945 .
15. Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K . Physiology of GDF9 and BMP15 signalling molecules . . 82-83 . 447–60 . 2004. 15271472 . 10.1016/j.anireprosci.2004.04.021.
16. Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O . Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture . J Clin Endocrinol Metab . 87 . 1 . 316–21 . 2002 . 11788667 . 10.1210/jcem.87.1.8185. free .
17. Hino J, Kangawa K, Matsuo H, Nohno T, Nishimatsu S . Bone morphogenetic protein-3 family members and their biological functions . Front Biosci . 9 . 1–3. 1520–9 . 2004. 14977563 . 10.2741/1355. free .
18. Cunningham N, Jenkins N, Gilbert D, Copeland N, Reddi A, Lee S . Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3 . Growth Factors . 12 . 2 . 99–109 . 1995 . 8679252 . 10.3109/08977199509028956.
19. Andersson O, Reissmann E, Ibáñez C . Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis . EMBO Reports. 7 . 8 . 831–7 . 2006 . 16845371 . 10.1038/sj.embor.7400752 . 1525155.
20. Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, Calof A . Autoregulation of neurogenesis by GDF11 . Neuron . 37 . 2 . 197–207 . 2003 . 12546816 . 10.1016/S0896-6273(02)01172-8. 15399794 .
21. Kim J, Wu H, Lander A, Lyons K, Matzuk M, Calof A . GDF11 controls the timing of progenitor cell competence in developing retina . Science . 308 . 5730 . 1927–30 . 2005 . 15976303 . 10.1126/science.1110175. 2005Sci...308.1927K . 42002862 .
22. Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L . Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury . Shock . 23 . 6 . 543–8 . 2005 . 15897808.
23. Hsiao E, Koniaris L, Zimmers-Koniaris T, Sebald S, Huynh T, Lee S . Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury . Mol Cell Biol . 20 . 10 . 3742–51 . 2000 . 10779363 . 10.1128/MCB.20.10.3742-3751.2000 . 85678.
24. Ago T, Sadoshima J . GDF15, a cardioprotective TGF-beta superfamily protein . Circ Res . 98 . 3 . 294–7 . 2006 . 16484622 . 10.1161/01.RES.0000207919.83894.9d. free .