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The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue
Sebastian Gehlen-Breitbach1, Theresa Schmid1,2, Franziska Fröb1
1Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
International Journal of Oral Science
|April 6, 2023
Summary
The Tip60/Ep400 complex is crucial for facial development. Its disruption impairs cranial neural crest cell metabolism, leading to orofacial clefting.
Area of Science:
- Developmental biology
- Genetics
- Cell biology
Background:
- Cranial neural crest cells are vital for orofacial development.
- Mutations affecting these cells cause orofacial malformations like cleft lip and palate.
- Chromatin remodeling factors are essential for regulating gene expression during facial development.
Purpose of the Study:
- To investigate the role of the Tip60/Ep400 chromatin remodeling complex in orofacial development.
- To determine the impact of Kat5 and Ep400 inactivation on cranial neural crest cells.
Main Methods:
- CRISPR/Cas9-guided genome editing in mice.
- Conditional mutagenesis to inactivate Kat5 or Ep400.
- Analysis of cranial neural crest cell metabolism, proliferation, and survival.
Main Results:
- Inactivation of Kat5 or Ep400 severely impacts metabolism in cranial neural crest cells.
- This leads to reduced protein synthesis, proliferation, and survival.
- Loss of either protein results in a drastic reduction of neural crest cells and facial structure loss.
- Heterozygous Kat5 loss impairs palatogenesis.
Conclusions:
- The Tip60/Ep400 complex plays a decisive role in facial morphogenesis.
- Disruptions in cranial neural crest cells due to Tip60/Ep400 dysfunction contribute to orofacial clefting in patients with KAT5 mutations.
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