SHH E176/E177-Zn²⁺ conformation is required for signaling at endogenous sites.

ABSTRACT: Sonic hedgehog (SHH) is a master developmental regulator. In 1995, the SHH crystal structure predicted that SHH-E176 (human)/E177 (mouse) regulates signaling through a Zn²⁺-dependent mechanism. While Zn²⁺ is known to be required for SHH protein stability, a regulatory role for SHH-E176 or Zn²⁺ has not been described. Here, we show that SHH-E176/177 modulates Zn²⁺-dependent cross-linking in vitro and is required for endogenous signaling, in vivo. While ectopically expressed SHH-E176A is highly active, mice expressing SHH-E177A at endogenous sites (Shh^E177A/-) are morphologically indistinguishable from mice lacking SHH (Shh^-/-), with patterning defects in both embryonic spinal cord and forebrain. SHH-E177A distribution along t

SUBMITTER: Himmelstein DS 

PROVIDER: S-EPMC6047533 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature