Impaired intervertebral disc formation in the absence of Jun.
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.
Behrens
Axel
A
Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Haigh
Jody
J
Mechta-Grigoriou
Fatima
F
Nagy
Andras
A
Yaniv
Moshe
M
Wagner
Erwin F
EF
D000818:Animals; D000831:Animals, Newborn; D001824:Body Constitution / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics; D005141:Eyelid Diseases / Q000235:genetics; D005313:Fetal Death / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006801:Humans; D019426:Integrases / Q000235:genetics; D007403:Intervertebral Disc / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009672:Notochord / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012600:Scoliosis / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
C499177:COL2A1 protein, human; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D016755:Proto-Oncogene Proteins c-jun; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases