Col11a1a Expression Is Required for Zebrafish Development

The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations inCOL11A1. Zebrafish carry two copies of theCol11a1gene, designatedCol11a1aandCol11a1b.Col11a1ais located on zebrafish chromosome 24 andCol11a1bis located on zebrafish chromosome 2. Expression patterns are distinct forCol11a1aandCol11a1bandCol11a1ais most similar toCOL11A1that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse modelcho/cho. We investigated the function ofCol11a1ain craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel's cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene forCol11a1ais required for normal development and has similar functions to the mammalianCOL11A1gene. Due to its transparency, external fertilization, theCol11a1aknockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understandCol11a1-related early developmental events.