title: Comparison of hedgehog and patched-1 protein expression in the cranial sutures of craniosynostotic and wild-type rabbits.
abstract: Craniosynostosis is characterized by premature fusion of the cranial sutures. At the molecular level, mutations in homeobox genes, transcription factors, and growth factor receptors have been implicated in the pathogenesis of this disorder, but the specific etiologic pathways have not yet been elucidated. To further study the molecular biology behind craniosynostosis, perisutural tissues in a unique rabbit model with congenital delayed-onset coronal craniosynostosis were examined for the presence of the hedgehog family of growth factors and their receptor, patched-1. Expression of desert hedgehog, Indian hedgehog, sonic hedgehog, and patched-1 was evaluated in four areas: suture, endosteum, periosteum, and osteocytes, using immuno-histochemistry (n = 8). Protein levels in affected animals were compared with protein levels in wild-type control rabbits (n = 8). Overall, sonic hedgehog, Indian hedgehog, and patched-1 protein levels were greater in affected animals. Specifically, areas of increased staining were seen along the bony interface of the endosteum and periosteum and in the osteocytes of the synostotic rabbits. Interestingly, in the suture, increased levels of Indian hedgehog and sonic hedgehog, but not patched-1, were seen. There was minimal expression of desert hedgehog in both rabbit types. The increased overall presence of hedgehog and patched-1 proteins in synostotic rabbits may be a reactive change to the disorder or part of the pathogenic process. Although the specific cause cannot be determined from the data, it is clear that the molecular milieu of the cranial sutures in synostotic rabbits is markedly different from that of wild-type rabbits.
authors.affiliation: Joe DiMaggio Children's Hospital, Cranio Facial Center, Hollywood, Fla. 33021, USA.
authors.forename: Rhoda L
authors.initials: RL
authors.lastname: Nott
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stelnicki
authors.forename: Judith A
authors.initials: JA
authors.lastname: Mack
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ben
authors.forename: Ronal
authors.initials: R
authors.lastname: Mitchell
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003393:Cranial Sutures / Q000473:pathology*; D003398:Craniosynostoses / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D053823:Hedgehog Proteins; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D010011:Osteocytes / Q000473:pathology; D000072079:Patched Receptors; D010521:Periosteum / Q000473:pathology; D011247:Pregnancy; D011817:Rabbits; D011956:Receptors, Cell Surface; D015534:Trans-Activators / Q000032:analysis*
chemical_list: D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D015534:Trans-Activators