High impact information on Gdf11

• During early mouse embryogenesis, Gdf11 is expressed in the primitive streak and tail bud regions, which are sites where new mesodermal cells are generated [1].
• Mutant embryos show alterations in patterns of Hox gene expression, suggesting that Gdf11 acts upstream of the Hox genes [1].
• The effect of the mutation is dose dependent, as Gdf11+/- mice have a milder phenotype than Gdf11-/- mice [1].
• Homozygous mutant mice carrying a targeted deletion of Gdf11 exhibit anteriorly directed homeotic transformations throughout the axial skeleton and posterior displacement of the hindlimbs [1].
• This negative autoregulatory action of GDF11 is strikingly like that of its homolog, GDF8/myostatin, in skeletal muscle, suggesting that similar strategies establish and maintain proper cell number during neural and muscular development [2].

Biological context of Gdf11

• We also provide evidence that Gdf11 induces Smad2 phosphorylation and activated Smad2 is able to induce caudal Hox gene expression [3].
• We now report that Gdf11 also regulates kidney organogenesis [4].
• In situ hybridization of sections and whole-mount embryos demonstrated Gdf11 is first strongly expressed in restricted domains at 8.5 days post coitus (dpc) when it is highest in the tail bud [5].
• Our results show that TSA up-regulates the expression of the gene encoding growth-differentiation factor 11 (Gdf11), a transforming growth factor beta family member that inhibits cell proliferation [6].
• Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb [7].

Anatomical context of Gdf11

• Mice deficient for Gdf11 harbor increased numbers of NGN3+ cells, revealing that GDF11 negatively regulates production of islet progenitor cells [8].
• Gdf11 is expressed in embryonic pancreatic epithelium during formation of islet progenitor cells that express neurogenin 3 [8].
• The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord [3].
• Our previous study using an in vitro assay system demonstrated that Fgf and Gdf11 signals located around Hensen's node of chick embryos have the ability to induce profiled Hoxc protein expression [3].
• Our studies suggest that Gdf11 may be important in directing the initial outgrowth of the ureteric bud from the Wolffian duct by controlling the expression of Gdnf in the metanephric mesenchyme [4].

Associations of Gdf11 with chemical compounds

• We provide evidence that the convergent activities of FGFs, Gdf11, and retinoid signals originating from Hensen's node and paraxial mesoderm establish and refine the Hox-c positional identity of motor neurons in the developing spinal cord [9].

Regulatory relationships of Gdf11

• Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development [8].
• In addition, GDF11 induced the expression of its own antagonist follistatin, indicating that the activity of GFD11 may be limited by a negative feedback mechanism [7].

Other interactions of Gdf11

• The mature carboxyl-terminal domain encoded by Gdf11 is most closely related to Gdf8, being 90% identical to the mouse gene [5].
• The addition of Gdnf protein to urogenital tracts taken from Gdf11 null embryos induced ectopic ureteric bud formation along the Wolffian duct [4].
• We have cloned and characterized a new member of the bone morphogenetic protein/transforming growth factor beta (BMP/TGFbeta) superfamily, growth differentiation factor 11 (Gdf11), from rat incisor pulp RNA by reverse transcription-polymerase chain reaction using degenerate primers [5].
• Gdf11 and Bmp4 are essential for outgrowth and positioning of the ureteric bud, the inducer of metanephric mesenchyme [10].
• Mice lacking functional GDF11 have more progenitors and neurons in the OE, whereas mice lacking follistatin, a GDF11 antagonist, show dramatically decreased neurogenesis [2].

Analytical, diagnostic and therapeutic context of Gdf11

• Northern blot analysis revealed Gdf11 is expressed in adult dental pulp and brain [5].
• The Gdf11 cDNA plasmid which was transferred into mesenchymal cells derived from mouse dental papilla by electroporation, induced the expression of Dsp [11].
• Using in situ hybridization and reverse transcriptase-polymerase chain reaction analyses, we show that Gdf11 transcripts are expressed in embryonic pancreas epithelium before the secondary transition but decrease rapidly afterward [12].
• During embryonic development, real time PCR demonstrated increasing GDF11 mRNA levels 10 h post-fertilization (hpf), while MSTN mRNA levels remain low until 48 hpf [13].
• Chromatin immunoprecipitation assays showed that treatment of cells with TSA or silencing of HDAC3 expression by small interfering RNA causes the hyperacetylation of Lys-9 in histone H3 on the gdf11 promoter [6].

References