Runx2 function in cells of neural crest origin during intramembranous ossification
Yukako Shirai1, Kenji Kawabe1, Ikue Tosa1
1Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Biochemical and Biophysical Research Communications
|January 21, 2019
Summary
Runt-related transcription factor 2 (Runx2) is crucial for neural crest cell differentiation and craniofacial bone development. Runx2 deficiency impairs ossification in Wnt1-lineage cells, highlighting its essential role in intramembranous ossification.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Runt-related transcription factor 2 (Runx2) is a master gene for osteoblast differentiation, with known in vivo functions in mesoderm-derived cells.
- The role of Runx2 in neural crest (NC)-derived cell differentiation in vivo remains unexplored.
Purpose of the Study:
- To investigate the in vivo function of Runx2 during the differentiation of craniofacial neural crest-derived cells.
- To determine the necessity of Runx2 for intramembranous ossification in NC-derived cells.
Main Methods:
- Utilized Wnt1-Cre mice to specifically target Runx2 deficiency in Wnt1-expressing craniofacial NC-derived cells (Runx2wnt1-/-).
- Performed skeletal analysis on Runx2wnt1-/- and heterozygous (Runx2wnt1+/-) embryos to assess ossification defects.
Main Results:
- Runx2 deficiency in Wnt1 lineage cells led to defective ossification in anterior craniofacial bones (frontal, jugal, squamous temporal, mandible, maxilla, nasal).
- Heterozygous Runx2wnt1+/- embryos exhibited impaired frontal bone closure and lack of secondary palate despite normal ossification elsewhere.
- Central frontal bone ossification showed higher dependency on Runx2 compared to other cranial regions.
Conclusions:
- Runx2 is indispensable for the differentiation of both mesoderm- and NC-derived cells during intramembranous ossification.
- Craniofacial NC-derived cells exhibit varying levels of dependency on Runx2 for successful ossification based on their location.
- This study elucidates a critical role for Runx2 in craniofacial development originating from the neural crest.
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