title: Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.
abstract: METHODS
  The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles.
  
  
  OBJECTIVE
  To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice.
  
  
  BACKGROUND
  The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi.
  
  
  METHODS
  Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice.
  
  
  RESULTS
  Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi.
  
  
  CONCLUSIONS
  Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Maier
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055428:Growth Differentiation Factor 5 / Q000172:deficiency / Q000235:genetics*; D017403:In Situ Hybridization; D007403:Intervertebral Disc / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009672:Notochord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors
chemical_list: D055428:Growth Differentiation Factor 5