Fig. 1. GDF11 is predominantly expressed in the EN in the adult mouse, marmoset and human brain.

a–e Schematic diagrams of the brain of mouse (a), and the red box in the cerebral cortex shows the location where the images were taken. Immunofluorescence double labelling (b, c, 2 double-labelled neurons are indicated as examples in (b, c)) and quantification (d, e, n = 6 images from 3 mice) of GDF11 (green, b) and NeuN (red, b) or GDF11 (green, c) and CaMKIIα (red, c) in the cerebral cortices of the mice aged 3 months (3 M). f Representative images of immuno-electron microscopy (Immuno-EM) of GDF11 labelled with nanogold particles (there are many GDF11 labelled black dots and only some examples are indicated with red arrows) in the cerebral cortex of the mice aged 3 M (n = 3 mice). Nuc, nucleus; Den, dendrite. g Immunofluorescence double labelling of GDF11 (green, arrow) and GABA (red, double arrowheads) (n = 3 mice). h Immunofluorescence double labelling of GDF11 (green) together with Olig2 (red, left), GFAP (red, middle), Iba1 (red, middle) in the cerebral cortex (Cx) and Dcx (red, right) in the dentate gyrus (DG) of the mice aged 3 M (n = 3 mice). The GDF11 negative cells are indicated by arrows in (h). i Schematic diagrams of the brain of the marmoset (one aged 62 M and another aged 70 M), and the red box in the cerebral cortex shows the location of the images (n = 2 marmosets). j–o Immunofluorescence double labelling (j, m, n, o) and quantification (k, l) of GDF11 (green) together with CaMKIIα (red, j, k, l, 2 double-labelled neurons are indicated as examples in (j); n = 8 images from 2 marmosets) or GABA (red, m), Olig2 (red, n) or GFAP (red, o). The GDF11 negative cells are indicated by arrows in (m, n, q). p Schematic diagrams of the human brain. The red box in the cerebral cortex shows the location of the images. q–s Immunofluorescence double labelling (q, male patient aged 24 years (Y) and female patient aged 23Y diagnosed with intractable epilepsy and the focus of epileptic cortices had to be removed surgically) and quantification (r, s, n = 4 patients, male patient aged 23Y, male patient aged 52Y, female patient aged 54Y and male patient aged 60Y suffered brain injury) of GDF11 (green) together with CaMKIIα (red) in the cerebral cortex of patients and 2 double-labelled neurons are indicated by arrows in (q). t Immunofluorescence double labelling of GDF11 (green) together with GABA (red, left), Olig2 (red, middle), GFAP (red, middle) and Iba1 (red, right) in the cerebral cortex of patients (n = 4 patients). The GDF11 negative cells are indicated by arrows in (t). Scale bars, as shown on the images, 30 μm (b, c), 250 nm (f), 10 μm (g), 40 μm (j, m, n, o), 20 μm (h, q, t). Data are presented as mean ± SEM. Source data are provided with this paper.