Fig 2: Intra-ovarian distribution of TAF15 in human primordial and primary follicles. This showed detection of the TAF15 protein in both oocyte and granulosa cells of (A) primordial, (B) primary, and (C) secondary, as well as (D–F) small pre-antral/early antral follicles. Hoechst staining identifies the nucleus of cells. Scale bars; 30 μm.

Fig 3: A high-resolution map of TAF15 amyloid filaments from FTLD-FET.a, Fourier shell correlation (FSC) curves for two independently refined half maps from individual 1 (black line); for the refined atomic model against the cryo-EM density map (blue); and for the atomic model shaken and refined against the first (green) or second (red) independent half map. FSC thresholds of 0.143 and 0.5, as well as a vertical line at the estimated map resolution of 1.97 Å are plotted. b, The map viewed along the helical axis, showing well-resolved individual TAF15 molecules. c, The map with rainbow-coloured local resolution estimates viewed perpendicular to the helical axis. d, The map, shown at contour levels of 0.015 (orange) and 0.0345 (blue), viewed for a single TAF15 molecule perpendicular to the helical axis, shows a well-resolved backbone and clear side-chain densities, including aromatic rings of tyrosine residues.

Fig 4: FET proteins and transportin 1 in FTLD–FET.a, FUS, EWS, TAF15 and transportin 1 immunoreactivity (brown) in the prefrontal cortex of individials 1–4 with FTLD–FET. Sections were counterstained with haematoxylin (blue). Scale bar, 50 μm. Neuronal cytoplasmic inclusions were immunoreactive for FUS, TAF15 and transportin 1 (examples indicated by magenta arrows for individual 1). Antibodies against EWS showed diffuse labelling of nuclei only (example indicated by cyan arrow for individual 1). b, Immunoblots of the total homogenate, sarkosyl-soluble fraction and sarkosyl-insoluble fraction of frontotemporal cortex grey matter from individuals 1–4 with FTLD–FET with antibodies against FUS, EWS, TAF15 and transportin 1. Asterisks indicate bands corresponding to full-length proteins. Bands of lower molecular weight probably correspond to protease cleavage products. For uncropped images of immunoblots see Supplementary Fig. 1. a,b, Results are representative of n ≥ 3 technical replicates per individual.

Fig 5: Motor neuron pathology.a, b, Luxol fast blue staining of myelin in the thoracic (a) and lumbar (b) spinal cord of FTLD-FET individual 1 showing extensive corticospinal tract loss (cyan arrows). Scale bar, 1 mm. c–e, FUS, EWS, TAF15 and transportin 1 immunoreactivity (brown) in the spinal cord of individual 3 (c), the brainstem of individuals 1–4 (d); and the motor cortex of individuals 1–4 (e). Sections were counterstained with hematoxylin (blue). Scale bars, 50 μm. Abundant motor neuron inclusions were observed for individuals 1 and 4, whereas inclusions were scarce or absent in individuals 2 and 3. Motor neuron inclusions were immunoreactive for FUS, TAF15 and transportin 1. Antibodies against EWS only showed diffuse labelling of nuclei. For a–e, the results are representative of n ≥ 3 technical replicates per individual.