English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Hedgehog signaling is primarily transduced by two transcription factors: Gli2, which mainly acts as a full-length activator, and Gli3, which tends to be proteolytically processed from a full-length form (Gli3 FL ) to an N-terminal repressor (Gli3 REP ). Recent studies using a  Sufu  knockout mouse have indicated that Sufu is involved in regulating Gli2 and Gli3 activator and repressor activity at multiple steps of the signaling cascade; however, the mechanism of specific Gli2 and Gli3 regulation remains to be elucidated. In this study, we established an allelic series of ENU-induced mouse strains. Analysis of one of the missense alleles,  Sufu T396I  , showed that Thr 396  residue of Sufu played a key role in regulation of Gli3 activity.  Sufu T396I/T396I    embryos exhibited severe polydactyly, which is indicative of compromised  Gli3  activity. Concomitantly, significant quantitative reductions of unprocessed Gli3 (Gli3 FL ) and processed Gli3 (Gli3 REP ) were observed  in vivo  as well as  in vitro . Genetic experiments showed that patterning defects in the limb buds of  Sufu T396I/T396I   were rescued by a constitutive Gli3 REP  allele ( Gli3 ∆699  ), strongly suggesting that Sufu T396I  reduced the truncated Gli3 repressor. In contrast, Sufu T396I  qualitatively exhibited no mutational effects on Gli2 regulation. Taken together, the results of this study show that the Thr 396  residue of Sufu is specifically required for regulation of Gli3 but not Gli2. This implies a novel Sufu-mediated mechanism in which Gli2 activator and Gli3 repressor are differentially regulated.

T396I Mutation of Mouse Sufu Reduces the Stability and Activity of Gli3 Repressor