Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the mouse spinal cord

Hongchen Cai, Aimin Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)72-85
Number of pages14
JournalDevelopmental biology
Volume432
Issue number1
DOIs
StatePublished - Dec 1 2017

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Hedgehogs
Spinal Cord
Proteins
Hedgehog Proteins
Mutant Proteins
Ubiquitin-Protein Ligases
Ubiquitination
Interneurons
Transcription Factors
Phenotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

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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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Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the mouse spinal cord. / Cai, Hongchen; Liu, Aimin.

In: Developmental biology, Vol. 432, No. 1, 01.12.2017, p. 72-85.

Research output: Contribution to journalArticle

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