Fig. 6

Overexpression or pharmacological activation of pgk1 rescues motor neuron phenotypes in smn morphant zebrafish.

(A) Representative confocal micrographs of primary motor neuron axons exiting the spinal cord in control (top), smn morphant (middle) and smn morphant over-expressing pgk1 (bottom) Tg(hb9:GFP) zebrafish embryos. Note the presence of an axonal outgrowth/branching phenotype associated with smn knockdown (arrow heads) that is reduced in the pgk1 over-expressing animals. Scale bars = 50 μM. (B) Overexpression of Pgk1 in smn morphant zebrafish at 30 hpf led to a significant increase in normal motor axons and significant decrease in severe axonal outgrowth phenotypes compared to single smn MO injected embryos. (C) Representative confocal micrographs of motor neuron axons exiting the spinal cord in control (top), smn morphant (middle) and smn morphant treated with 2.5 μM terazosin (bottom) Tg(hb9:GFP) zebrafish embryos. Note how the presence of the axonal outgrowth/branching phenotype associated with smn knockdown (arrow heads) is reduced in the terazosin-treated animals. (D) Bar chart (mean & s.e.m) showing activation of Pgk1 by treatment with 2.5 μM terazosin in smn morphant zebrafish at 30 hpf led to a significant increase in normal motor axons and significant decrease in severe axonal outgrowth phenotypes compared to untreated smn MO injected embryos. Unpaired two-tailed student t-tests * p<0.05, ** p<0.01 *** p<0.001. n = 20 embryos per group.