Spop Regulates Gli3 Activity and Shh Signaling in Dorsoventral Patterning of the Mouse Spinal Cord

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2017 Apr 17

PMID 28412462

Citations 16

Authors

Hongchen Cai

Aimin Liu

Affiliations

Soon will be listed here.

Abstract

Sonic Hedgehog (Shh) signaling regulates the patterning of ventral spinal cord through the effector Gli family of transcription factors. Previous in vitro studies showed that an E3 ubiquitin ligase containing Speckle-type POZ protein (Spop) targets Gli2 and Gli3 for ubiquitination and degradation, but the role of Spop in Shh signaling and mammalian spinal cord patterning remains unknown. Here, we show that loss of Spop does not alter spinal cord patterning, but it suppresses the loss of floor plate and V3 interneuron phenotype of Gli2 mutants, suggesting a negative role of Spop in Gli3 activator activity, Shh signaling and the specification of ventral cell fates in the spinal cord. This correlates with a moderate but significant increase in the level of Gli3 protein in the Spop mutant spinal cords. Furthermore, loss of Spop restores the maximal Shh pathway activation and ventral cell fate specification in the Gli1;Sufu double mutant spinal cord. Finally, we show that loss of Spop-like does not change the spinal cord patterning in either wild type or Spop mutants, suggesting that it does not compensate for the loss of Spop in Shh signaling and spinal cord patterning. Therefore, our results demonstrate a negative role of Spop in the level and activity of Gli3, Shh signaling and ventral spinal cord patterning.

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