title: Molecular signaling in intervertebral disk development.
abstract: The purpose of this investigation is to identify and study the expression pattern of pertinent molecular factors involved in the differentiation of the intervertebral disk (IVD). It is likely that hedgehog genes and the BMP inhibitors are key factors involved in spinal joint formation. Radioactive in situ hybridization with mRNA probes for pax-1, SHH, IHH and Noggin gene was performed on mouse embryo and adult tissue. Immunohistochemistry was performed to localize hedgehog receptor, "patched" (ptc). From 14.5 dpc until birth pax-1 mRNA was expressed in the developing anulus fibrosus (AF). During the same developmental period Noggin mRNA is highly expressed throughout the spine, in the developing AF, while ptc protein and SHH mRNA were expressed in the developing nucleus pulposus (NP). IHH mRNA was expressed by condensing chondrocytes of the vertebral bodies and later becomes confined to the vertebral endplate. We show for the first time that pax-1 is expressed in the adult intervertebral disk. Ptc expression in the NP is an indicator of hedgehog protein signaling in the developing IVD. The expression pattern of the BMP inhibitor Noggin appears to be important for the normal formation of the IVD and may prove to play a role in its segmental pattern formation.
authors.affiliation: Department of Orthopaedics, Cornell University Medical College, University of Rochester Medical Center, Rochester, NY 14642, USA. cpd62@yahoo.com
authors.forename: Christian P
authors.initials: CP
authors.lastname: DiPaola
authors.forename: James C
authors.initials: JC
authors.lastname: Farmer
authors.forename: Katia
authors.initials: K
authors.lastname: Manova
authors.forename: Lee A
authors.initials: LA
authors.lastname: Niswander
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D053823:Hedgehog Proteins; D007403:Intervertebral Disc / Q000196:embryology*; D051379:Mice; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D000099176:Noggin Protein; C465570:Shh protein, mouse; C070835:PAX1 transcription factor