Growth differentiation factor

Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development.cite journal |author=Herpin A, Lelong C, Favrel P |title=Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans |journal=Dev Comp Immunol |volume=28 |issue=5 |pages=461–85 |year=2004 |pmid=15062644 |doi=10.1016/j.dci.2003.09.007]

Types

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

* GDF1 is chiefly expressed in the nervous system and functions in left-right patterning and mesoderm induction during embryonic development. [cite journal |author=Rankin C, Bunton T, Lawler A, Lee S |title=Regulation of left-right patterning in mice by growth/differentiation factor-1 |journal=Nat Genet |volume=24 |issue=3 |pages=262–5 |year=2000 |pmid=10700179 |doi=10.1038/73472]
* 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.cite journal |author=Lopez-Coviella I, Follettie M, Mellott T, Kovacheva V, Slack B, Diesl V, Berse B, Thies R, Blusztajn J |title=Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons |journal=Proc Natl Acad Sci U S A |volume=102 |issue=19 |pages=6984–9 |year=2005 |pmid=15870197 |doi=10.1073/pnas.0502097102] [cite journal |author=Truksa J, Peng H, Lee P, Beutler E |title=Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6 |journal=Proc Natl Acad Sci U S A |volume=103 |issue=27 |pages=10289–93 |year=2006 |pmid=16801541 |doi=10.1073/pnas.0603124103]
* 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. [cite journal |author=Levine A, Brivanlou A |title=GDF3 at the crossroads of TGF-beta signaling |journal=Cell Cycle |volume=5 |issue=10 |pages=1069–73 |year=2006 |pmid=16721050] [cite journal |author=Levine A, Brivanlou A |title=GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos |journal=Development |volume=133 |issue=2 |pages=209–16 |year=2006 |pmid=16339188 |doi=10.1242/dev.02192] [cite journal |author=Chen C, Ware S, Sato A, Houston-Hawkins D, Habas R, Matzuk M, Shen M, Brown C |title=The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo |journal=Development |volume=133 |issue=2 |pages=319–29 |year=2006 |pmid=16368929 |doi=10.1242/dev.02210]
*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. [cite journal |author=O'Keeffe G, Dockery P, Sullivan A |title=Effects of growth/differentiation factor 5 on the survival and morphology of embryonic rat midbrain dopaminergic neurones in vitro |journal=J Neurocytol |volume=33 |issue=5 |pages=479–88 |year=2004 |pmid=15906156 |doi=10.1007/s11068-004-0511-y] [cite journal |author=Buxton P, Edwards C, Archer C, Francis-West P |title=Growth/differentiation factor-5 (GDF-5) and skeletal development |journal=J Bone Joint Surg Am |volume=83-A Suppl 1 |issue=Pt 1 |pages=S23–30 |year=2001 |pmid=11263662] [cite journal |author=Francis-West P, Parish J, Lee K, Archer C |title=BMP/GDF-signalling interactions during synovial joint development |journal=Cell Tissue Res |volume=296 |issue=1 |pages=111–9 |year=1999 |pmid=10199971 |doi=10.1007/s004410051272]
*GDF6 interacts with bone morphogenetic proteins to regulate ectoderm patterning, and controls eye development. [cite journal |author=Chang C, Hemmati-Brivanlou A |title=Xenopus GDF6, a new antagonist of noggin and a partner of BMPs |journal=Development |volume=126 |issue=15 |pages=3347–57 |year=1999 |pmid=10393114] [cite journal |author=Asai-Coakwell M, French C, Berry K, Ye M, Koss R, Somerville M, Mueller R, van Heyningen V, Waskiewicz A, Lehmann O |title=GDF6, a novel locus for a spectrum of ocular developmental anomalies |journal=Am J Hum Genet |volume=80 |issue=2 |pages=306–15 |year=2007 |pmid=17236135 |doi=10.1086/511280] [cite journal |author=Hanel M, Hensey C |title=Eye and neural defects associated with loss of GDF6 |journal=BMC Dev Biol |volume=6 |issue= |pages=43 |year= |pmid=17010201 |doi=10.1186/1471-213X-6-43]
* GDF8 is now officially known as myostatin and controls the growth of muscle tissue. [McPherron AC, Lawler AM, Lee SJ. "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member." Nature 1997;387:83-90. PMID 9139826.]
* 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. [cite journal |author=Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K |title=Physiology of GDF9 and BMP15 signalling molecules |journal=Anim Reprod Sci |volume=82-83 |issue= |pages=447–60 |year= |pmid=15271472 |doi=10.1016/j.anireprosci.2004.04.021] [cite journal |author=Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O |title=Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture |journal=J Clin Endocrinol Metab |volume=87 |issue=1 |pages=316–21 |year=2002 |pmid=11788667 |doi=10.1210/jc.87.1.316]
*GDF10 is closely related to BMP3 and has a roles in head formation and possibly in skeletal morphogenesis. [cite journal |author=Hino J, Kangawa K, Matsuo H, Nohno T, Nishimatsu S |title=Bone morphogenetic protein-3 family members and their biological functions |journal=Front Biosci |volume=9 |issue= |pages=1520–9 |year= |pmid=14977563 |doi=10.2741/1355] cite journal |author=Cunningham N, Jenkins N, Gilbert D, Copeland N, Reddi A, Lee S |title=Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3 |journal=Growth Factors |volume=12 |issue=2 |pages=99–109 |year=1995 |pmid=8679252 |doi=10.3109/08977199509028956] It is also known as BMP-3b.
*GDF11 controls anterior-posterior patterning by regulating the expression of Hox genes,cite journal |author=Andersson O, Reissmann E, Ibáñez C |title=Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis |journal=EMBO Rep |volume=7 |issue=8 |pages=831–7 |year=2006 |pmid=16845371 |doi=10.1038/sj.embor.7400752] and regulates the number of olfactory receptor neurons occurring in the olfactory epithelium, [cite journal |author=Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, Calof A |title=Autoregulation of neurogenesis by GDF11 |journal=Neuron |volume=37 |issue=2 |pages=197–207 |year=2003 |pmid=12546816 |doi=10.1016/S0896-6273(02)01172-8] and numbers of retinal ganglionic cells developing in the retina. [cite journal |author=Kim J, Wu H, Lander A, Lyons K, Matzuk M, Calof A |title=GDF11 controls the timing of progenitor cell competence in developing retina |journal=Science |volume=308 |issue=5730 |pages=1927–30 |year=2005 |pmid=15976303 |doi=10.1126/science.1110175]
*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.cite journal |author=Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L |title=Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury |journal=Shock |volume=23 |issue=6 |pages=543–8 |year=2005 |pmid=15897808] cite journal |author=Hsiao E, Koniaris L, Zimmers-Koniaris T, Sebald S, Huynh T, Lee S |title=Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury |journal=Mol Cell Biol |volume=20 |issue=10 |pages=3742–51 |year=2000 |pmid=10779363 |doi=10.1128/MCB.20.10.3742-3751.2000] [cite journal |author=Ago T, Sadoshima J |title=GDF15, a cardioprotective TGF-beta superfamily protein |journal=Circ Res |volume=98 |issue=3 |pages=294–7 |year=2006 |pmid=16484622 |doi=10.1161/01.RES.0000207919.83894.9d]

References