Snu13 genes are essential for embryonic development past early segmentation stages

Snu13 function is necessary for full activity of the core spliceosome, acting via the U4 snRNP complex. When snu13 function was hypomorphically reduced in drosophila, the resulting embryos displayed severe muscle defects. To investigate the possibility that Snu13 has a specific role in vertebrate muscle development we generated knockout lines for the two zebrafish snu13 orthologs, snu13a and snu13b. Initial F2 generation analysis suggested that fish require at least one snu13 gene for viability. We then outcrossed the fish for several subsequent generations and in-crossed to confirm this requirement. Only double mutant fish appear abnormal and snu13a fish are homozygous viable, even when heterozygous also for snu13b (snu13a-/-;snu13b-/+), suggesting that the two genes act in a largely redundant fashion. Double mutant embryos (snu13a-/-;snu13b-/-) appeared normal until 10 hours post fertilization (hpf), but their development ceases to progress by 12 hpf. The initial phase of normal development (0-10 hpf) may be enabled by maternal snu13 expression, which has been demonstrated in the EMBL-EBI RNA Seq repository. At 24 hpf the double mutant fish are easily distinguished from the wild type (Figure 1). The snu13a;snu13b double mutant possesses head (blue) and tail (orange) primordia, however, these two primordia have not elaborated beyond their morphology in early somitogenesis and have become necrotic. A severe halt to snu13a-/-;snu13b-/- double mutant development during early somitogenesis is consistent with protein function in the core spliceosome, which globally impacts embryogenesis.