1. A novel cis-regulatory element drives early expression ofiNkx3.2/iin the gnathostome primary jaw joint
- Author
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Jake, Leyhr, Laura, Waldmann, Beata, Filipek-Górniok, Hanqing, Zhang, Amin, Allalou, and Tatjana, Haitina
- Subjects
Mammals ,Genome ,Jaw ,Vertebrates ,Animals ,Lampreys ,Gene Expression Regulation, Developmental ,Regulatory Sequences, Nucleic Acid ,Biological Evolution ,Zebrafish ,Gene Deletion - Abstract
The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element ofiNkx3.2/ithat is deeply conserved in most gnathostomes but undetectable in the jawless hagfish and lamprey. This enhancer is active in the developing jaw joint region of the zebrafishiDanio rerio/i, and was thus designated asijaw joint regulatory sequence 1/i(JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 results in a significant reduction of early gene expression ofinkx3.2/iand leads to a transient jaw joint deformation and partial fusion. Emergence of thisiNkx3.2/ienhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws. more...
- Published
- 2021