A hitherto unidentified N-ethyl-N-nitrosourea (ENU)-induced mutation affects dorsal root ganglia (DRG) formation in ouchless mutant zebrafish larvae. In contrast to previous findings assigning the ouchless phenotypes to downregulated sorbs3 transcript levels, this work re-attributes the phenotypes to an essential splice site mutation affecting adgra2 (gpr124) splicing and function. Accordingly, ouchless mutants fail to complement previously characterized adgra2 mutants and exhibit highly penetrant cerebrovascular defects. The aberrantly spliced adgra2 transcript found in ouchless mutants encodes a receptor lacking a single leucine-rich repeat (LRR) within its N-terminus.
The authors declare no competing or financial interests.
N.B. is supported by a FRIA fellowship from Fonds de la Recherche Scientifique - FNRS. Work in the B.V. laboratory is supported by the FNRS (MIS F.4543.15), a Concerted Research Action (ARC) grant from the Fédération Wallonie-Bruxelles and the Fondation Université libre de Bruxelles. The Center for Microscopy and Molecular Imaging (CMMI) is supported by the European Regional Development Fund (ERDF).