Fig 1

polr3a^sa907 disrupts craniofacial development.
(A) Representation of the exons of polr3a in zebrafish. The sa907 allele is in exon 14 (magenta arrow). (B) Schematic of protein domains of human POLR3A (based on Girbig et al., 2021). The amino acid sequence encoded by exon 14 is highlighted in purple, located in the pore domain. (C) Location of pathogenic variants within the protein domain encoded by exon 14 associated with POLR3-related leukodystrophy (black), WRS (blue), and the location of sa907 (magenta). (D) Representation of the 17-subunit RNA Polymerase III complex highlighting POLR3A, magenta. (E-I) Brightfield images at 5 dpf shows an overall change in the size of the head, including the jaw (arrows; E,H). Ventral views (F, I) show the overall length and width of the head is reduced. (G) qRT-PCR shows that the sa907 allele results in a significant reduction in polr3a mRNA expression in polr3a^sa907/sa907 homozygous mutant zebrafish at 3 dpf, and a slight reduction in polr3a^sa907/+ heterozygous zebrafish. ****p < 0.0001; ***p = 0.0005. (J-O) Alcian blue and Alizarin red staining shows overall reduction in the elements of the viscerocranium (K, N). Reductions in cartilage and bone elements including the opercle (op), Meckel’s cartilage (M), and the ceratohyal (ch), entopterygoid (en), and branchiostegal rays (bsr) are apparent by 5 dpf (L, O). Scale bar = 100 µm. Panel D Created in BioRender. Watt, K. (2026) https://BioRender.com/j5w61o1.