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Published on: December 3, 2016
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MEMO1 drives cranial endochondral ossification and palatogenesis
Eric Van Otterloo1, Weiguo Feng1, Kenneth L Jones2
1Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Developmental Biology
|January 10, 2016
Summary
A mutation in the Memo1 gene causes defects in cranial base development and cleft palate in mice. This study reveals Memo1
Area of Science:
- Developmental biology
- Genetics
- Craniofacial research
Background:
- The cranial base is crucial for integrating the face, brain, and vertebral column.
- Cranial base shape is linked to primate evolution and human facial abnormalities.
- Defects in cranial base development can lead to significant craniofacial dysmorphies.
Purpose of the Study:
- To investigate the role of the Memo1 gene in cranial base and palate development.
- To identify the function of Memo1 in craniofacial morphogenesis.
- To understand the genetic basis of craniofacial abnormalities.
Main Methods:
- Generated and analyzed a novel recessive mutant mouse strain with cranial base and palate defects.
- Performed gene mapping and non-complementation studies to identify the causative mutation in Memo1.
- Conducted expression analysis of Memo1 in developing cranial base and palatal shelves.
- Utilized neural crest cell-specific deletion of Memo1 to assess cell-autonomous roles.
- Examined gene expression related to bone formation, cartilage development, vascularization, and mineralization.
Main Results:
- A mutation in Memo1 caused defective cranial base formation and cleft secondary palate in mice.
- Memo1 is robustly expressed in the developing cranial base but modestly in palatal shelves.
- Mutant cranial bases showed reduced expression of bone formation genes and increased cartilage markers.
- Mutant cranial bases exhibited an expanded hypertrophic chondrocyte zone with impaired vascularization and mineralization.
- Neural crest cell-specific deletion of Memo1 impaired anterior cranial base ossification, indicating a cell-autonomous role.
- Palate formation was largely normal in conditional mutants, suggesting a non-autonomous role for Memo1 in palatal closure.
Conclusions:
- Memo1 plays a critical, cell-autonomous role in endochondral ossification of the cranial base.
- Memo1 also has a non-autonomous role in secondary palate closure.
- Defects in cranial base development due to Memo1 mutation have widespread effects on craniofacial shape.
- This study identifies a novel function for Memo1 in craniofacial development and links it to human craniofacial dysmorphies.
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