contributes to the midbrain development via Sonic Hedgehog signaling pathway in zebrafish embryos.

TRIM46 is a RING finger E3 ligase which belongs to TRIM (tripartite motif-containing) protein family. TRIM46 is required for neuronal polarity and axon specification by driving the formation of parallel microtubule arrays, whereas its embryological functions remain to be determined yet. Expression patterns and biological functions of , a zebrafish homologue of TRIM46, were studied in zebrafish embryo. First, maternal transcripts of were present at 1 cell stage whereas zygotic messages were abundant in the eyes, MHB (Midbrain-Hindbrain Boundary) and hindbrain at 24 hpf (hours post fertilization). Second, transcriptional regulatory region of contains -acting elements binding a transcriptional factor Foxa2. Transcription of is positively regulated by Sonic Hedgehog (SHH), and treatment of cyclopamine, an SHH inhibitor, represses transcription of in 4 hpf through 24 hpf embryos. Third, the transcriptional repression of inhibited transcription of to cause developmental defects in the midbrain and MHB. Finally, spatiotemporal expression patterns of a midbrain marker in the developmental defects confirmed inhibition of SHH by cyclopamine caused underdevelopment of the midbrain and MHB at 24 hpf. We propose a signaling network where contributes to development of the midbrain and MHB via Foxa2, a downstream element of SHH signaling in zebrafish embryogenesis.