Craniosynostosis, the premature closure of cranial suture, is a pathologic 
condition that affects 1/2000 live births. Saethre-Chotzen syndrome is a genetic 
condition characterized by craniosynostosis. The Saethre-Chotzen syndrome, which 
is defined by loss-of-function mutations in the TWIST gene, is the second most 
prevalent craniosynostosis. Although much of the genetics and phenotypes in 
craniosynostosis syndromes is understood, less is known about the underlying 
ossification mechanism during suture closure. We have previously demonstrated 
that physiological closure of the posterior frontal suture occurs through 
endochondral ossification. Moreover, we revealed that antagonizing canonical 
Wnt-signaling in the sagittal suture leads to endochondral ossification of the 
suture mesenchyme and sagittal synostosis, presumably by inhibiting Twist1. 
Classic Saethre-Chotzen syndrome is characterized by coronal synostosis, and the 
haploinsufficient Twist1(+/-) mice represents a suitable model for studying this 
syndrome. Thus, we seeked to understand the underlying ossification process in 
coronal craniosynostosis in Twist1(+/-) mice. Our data indicate that coronal 
suture closure in Twist1(+/-) mice occurs between postnatal day 9 and 13 by 
endochondral ossification, as shown by histology, gene expression analysis, and 
immunohistochemistry. In conclusion, this study reveals that coronal 
craniosynostosis in Twist1(+/-) mice occurs through endochondral ossification. 
Moreover, it suggests that haploinsufficiency of Twist1 gene, a target of 
canonical Wnt-signaling, and inhibitor of chondrogenesis, mimics conditions of 
inactive canonical Wnt-signaling leading to craniosynostosis.