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Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3
Dallas C Jones1, Michelle N Schweitzer, Marc Wein
1Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115, USA. djones@hsph.harvard.edu
Abstract:
Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mutations in the adapter proteins Schnurri2 (Shn2) and Schnurri3 (Shn3) exhibit defects in patterning of the axial skeleton during embryogenesis. Postnatally, these compound mutant mice develop a unique osteochondrodysplasia. The deletion of Shn2 and Shn3 impairs growth plate maturation during endochondral ossification but simultaneously results in massively elevated trabecular bone formation. Hence, growth plate maturation and bone formation can be uncoupled under certain circumstances. These unexpected findings demonstrate that both unique and redundant functions reside in the Schnurri protein family that are required for proper skeletal patterning and remodeling.
Insights
Mice lacking Schnurri2 and Schnurri3 proteins show skeletal patterning defects and a unique bone disorder. This study reveals distinct and overlapping roles for these proteins in skeletal development and remodeling.
Area of Science:
- Skeletal Biology
- Developmental Biology
- Genetics
Background:
- Skeletal formation and remodeling depend on precise gene regulation in cartilage and bone cells.
- Mutations disrupting these genetic programs cause skeletal diseases.
Purpose of the Study:
- To investigate the roles of Schnurri2 (Shn2) and Schnurri3 (Shn3) adapter proteins in skeletal development.
- To understand the consequences of combined Shn2 and Shn3 loss on skeletal patterning and bone formation.
Main Methods:
- Analysis of mice with parallel null mutations in Shn2 and Shn3.
- Examination of skeletal patterning during embryogenesis.
- Assessment of postnatal skeletal phenotypes, including growth plate maturation and bone formation.
Main Results:
- Compound Shn2/Shn3 mutant mice displayed defects in axial skeleton patterning during embryogenesis.
- Postnatal mice developed a unique osteochondrodysplasia characterized by impaired growth plate maturation.
- Simultaneously, massively elevated trabecular bone formation was observed, uncoupling growth plate maturation and bone formation.
Conclusions:
- Schnurri proteins (Shn2 and Shn3) have both unique and redundant functions essential for skeletal patterning and remodeling.
- The study demonstrates that growth plate maturation and bone formation can be dissociated.
- These findings highlight the complex regulatory mechanisms governing skeletal development.
