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Single-cell analysis identifies a key role for Hhip in murine coronal suture development
Greg Holmes1, Ana S Gonzalez-Reiche2,3, Madrikha Saturne2
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. gregory.holmes@mssm.edu.
Nature Communications
|December 9, 2021
Summary
Hedgehog signaling inhibitor Hhip is crucial for coronal suture development. Its absence in mice leads to abnormal suture closure and depleted mesenchyme, impacting skull bone growth.
Area of Science:
- Developmental biology
- Craniofacial development
- Molecular signaling
Background:
- Craniofacial development relies on skull bone sutures.
- Sutures comprise osteogenic fronts and mesenchyme for growth.
- Hedgehog signaling plays a role in skeletal development.
Purpose of the Study:
- To define the cellular populations within the embryonic murine coronal suture.
- To investigate the role of Hhip in coronal suture development.
- To understand the impact of hedgehog signaling on suture maintenance.
Main Methods:
- Single-cell RNA sequencing of wild-type murine coronal sutures at E16.5 and E18.5.
- Cell population analysis and identification.
- Genetic manipulation (Hhip knockout) and lineage tracing.
Main Results:
- Identified seven to nine distinct cell populations in the coronal suture mesenchyme and osteogenic fronts.
- Discovered Hhip marks a unique mesenchymal population.
- Observed that Hhip deficiency leads to fused osteogenic fronts and altered mesenchyme with increased hedgehog signaling.
Conclusions:
- Hhip is essential for normal coronal suture formation and maintenance.
- Hhip regulates cell populations and hedgehog signaling within the suture.
- Hhip-expressing cells contribute to long-term calvarial bone growth.
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