Related Experiment Video

Updated: May 23, 2025

Separation of Mouse Embryonic Facial Ectoderm and Mesenchyme
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Published on: April 12, 2013

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Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development

Shicheng Zhu1, Suman Huo1, Weiran He1

  • 1College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

Iscience
|March 12, 2025
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) regulates craniofacial development. Smg5 loss in neural crest cells causes mandible hypoplasia, cleft palate, and disrupts Wnt signaling via Porcn regulation.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial RNA quality control pathway.
  • The role of NMD in mammalian craniofacial development is not well understood.

Purpose of the Study:

  • To investigate the function of the NMD factor Smg5 in mouse craniofacial neural crest cell development.
  • To elucidate the molecular mechanisms by which Smg5 influences craniofacial morphogenesis.

Main Methods:

  • CRISPR-Cas9 mediated knockout of Smg5 in mouse craniofacial neural crest cells.
  • Analysis of craniofacial morphology, cell apoptosis, differentiation, and alternative splicing.
  • Assessment of Porcn transcript levels and Wnt5a/JNK signaling pathway activity.

Main Results:

  • Smg5 knockout led to hypoplastic mandibles, tongue mispositioning, and cleft palate.
  • Smg5 deficiency caused increased apoptosis, disrupted cell differentiation, and altered splicing.
  • Upregulation of a premature termination codon (PTC)-containing Porcn transcript reduced Porcn protein and impaired Wnt5a/JNK signaling.

Conclusions:

  • Smg5-mediated NMD is essential for mammalian craniofacial development.
  • Smg5 regulates craniofacial morphogenesis by controlling Porcn expression and Wnt signaling.
  • Targeting NMD pathways may offer therapeutic strategies for craniofacial developmental disorders.
Keywords:
Cell biologyDevelopmental biologyPathophysiology

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