XB-ART-61870
Development
2026 Jun 15; doi: 10.1242/dev.205428.
Show Gene links
Show Anatomy links
SIX1 BOR variants have different effects on embryonic craniofacial gene expression and cartilage formation.
???displayArticle.abstract???
SIX1 variants underlying Branchio-oto-renal syndrome occur in the SIX domain (SD) or homeodomain (HD). We tested whether different variants - V17E (SD), Y129C (HD) - cause distinct developmental phenotypes in embryos with reduced Six1 in comparison to wildtype Six1 (Six1WT). In Six1-morphants, Six1WT restored neural crest and preplacodal gene expression; V17E restored foxd3 and irx1 better than Y129C and Y129C restored sox11 better. In six1-null otic vesicles, Six1WT partially restored tbx1 and sobp, V17E was less effective and Y129C was least effective; all three restored dlx5. In six1-heterozygotes, Six1WT and Y129C had similar pleiotropic effects on tbx1, whereas V17E had no effect; Six1WT restored dlx5 expression, V17E was less effective and Y129C was most deficient. In six1-null tadpoles, reduced cranial cartilage volume and individual cartilage abnormalities were rescued by Six1WT, less so by V17E and not by Y129C. In heterozygotes and wildtypes, Y129C caused a higher frequency of abnormal cartilages compared to Six1WT or V17E. Thus, variants with different functional deficits have distinguishable effects in both nulls and heterozygotes on the formation of the tissues affected in Branchio-oto-renal syndrome.
???displayArticle.pubmedLink??? 42290293
???displayArticle.link??? Development
???displayArticle.grants???