Fig. 1

Expression of mutTARDBP results in touch-evoked defects in locomotor pattern generation. (Ai), Schematic representation of human wild type TARDBP and mutant TARDBP encoding the ALS-causing missense mutation G348C situated in the C-terminal glycine rich region. Other general structures of TARDBP include an N-terminal nuclear localization motif (L), RNA binding domains (RRM1 and RRM2) and a proposed nuclear export motif (E). (Aii–Aiv), Representative images of 52–54 hpf zebrafish larvae. Scale bar represents 1 mm. (B) Example still frames from high speed video recordings of touch-evoked locomotor tail-beat patterns in zebrafish larvae. Tail-beat patterns were found to be reduced in tail beat duration (C) and mean frequency (D) when compared to either wild type zebrafish or zebrafish larvae expressing wtTARDBP. Defects in pattern generation were observed in the synaptic inputs to muscle cells of the trunk during fictive locomotor patterns. (E) Example traces of whole-cell patch clamp recordings of rhythmic fast-twitch EPCs evoked by a light touch to the tail. No differences were found between the tail touch and the start of the EPCs (F), but the maximum EPC amplitude (G), mean EPC frequency (H) as well as the EPC burst duration (I) were all found to be reduced in larvae expressing mutTARDBP. Numbers in parentheses represent sample sizes. Asterisks and daggers represent statistical differences from wild type (p < 0.05) and wtTARDBP (p < 0.05) larvae respectively.