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Impaired intervertebral disc formation in the absence of Jun
Axel Behrens1, Jody Haigh, Fatima Mechta-Grigoriou
1Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Abstract:
Jun is a major component of the heterodimeric transcription factor AP-1 and is essential for embryonic development, as foetuses that lack Jun die at mid-gestation. Ubiquitous mosaic inactivation of a conditional Jun allele by cre/LoxP-mediated recombination was used to screen for novel functions of Jun and revealed that its absence results in severe malformations of the axial skeleton. More-specific Jun deletion by collagen2a1-cre demonstrated the essential function of Jun in the notochord and sclerotome. Mutant notochordal cells showed increased apoptosis, resulting in hypocellularity of the intervertebral discs. Subsequently, fusion of vertebral bodies caused a scoliosis of the axial skeleton. Thus, Jun is required for axial skeletogenesis by regulating notochord survival and intervertebral disc formation.
Insights
The transcription factor Jun is crucial for embryonic development and axial skeleton formation. Its absence leads to notochord cell death, abnormal intervertebral discs, and scoliosis.
Area of Science:
- Developmental Biology
- Genetics
- Skeletal Biology
Background:
- Jun is a key component of the AP-1 transcription factor, vital for embryonic development.
- Complete absence of Jun leads to embryonic lethality by mid-gestation.
Purpose of the Study:
- To investigate novel functions of Jun using conditional inactivation.
- To elucidate the role of Jun in axial skeleton development.
Main Methods:
- Utilized cre/LoxP-mediated recombination for ubiquitous mosaic inactivation of a conditional Jun allele.
- Employed collagen2a1-cre for specific Jun deletion in the notochord and sclerotome.
Main Results:
- Jun deficiency caused severe axial skeleton malformations.
- Specific deletion in notochord/sclerotome led to increased notochordal cell apoptosis and hypocellular intervertebral discs.
- Vertebral body fusion resulted in scoliosis.
Conclusions:
- Jun is essential for axial skeletogenesis.
- Jun regulates notochord cell survival and intervertebral disc formation, preventing vertebral defects.