| First Author | Himmelstein DS | Year | 2017 |
| Journal | Dev Biol | Volume | 424 |
| Issue | 2 | Pages | 221-235 |
| PubMed ID | 28263766 | Mgi Jnum | J:241009 |
| Mgi Id | MGI:5897497 | Doi | 10.1016/j.ydbio.2017.02.006 |
| Citation | Himmelstein DS, et al. (2017) SHH E176/E177-Zn2+ conformation is required for signaling at endogenous sites. Dev Biol 424(2):221-235 |
| abstractText | 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 (ShhE177A/-) are morphologically indistinguishable from mice lacking SHH (Shh-/-), with patterning defects in both embryonic spinal cord and forebrain. SHH-E177A distribution along the embryonic spinal cord ventricle is unaltered, suggesting that E177 does not control long-range transport. While SHH-E177A association with cilia basal bodies increases in embryonic ventral spinal cord, diffusely distributed SHH-E177A is not detected. Together, these results reveal a novel role for E177-Zn2+ in regulating SHH signaling that may involve critical, cilia basal-body localized changes in cross-linking and/or conformation. |
