Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation.
A classically identified "notochordal" cell population in the nucleus pulposus is thought to regulate disk homeostasis. However, the embryonic origin of these cells has been under dispute for >60 years. Here we provide the first direct evidence that all cell types in the adult mouse nucleus pulposus are derived from the embryonic notochord. Additionally, rare isolated embryonic notochord cells remained in the vertebral column and resembled "notochordal remnants," which in humans have been proposed to give rise to a rare type of late-onset cancer called chordoma. Previously, this cell type had not been identified in the mouse model system. The development and characterization of a mouse model that can be used to fate map nucleus pulposus precursor cells in any mutant background will be useful for uncovering the cellular and molecular mechanisms of disk degeneration. In addition, the identification of notochordal remnants in mice is the first step towards generating an in vivo model of chordoma.
Choi
Kyung-Suk
KS
Department of Molecular Genetics, University of Florida, College of Medicine, Gainesville, Florida 32610, USA.
Cohn
Martin J
MJ
Harfe
Brian D
BD
D000375:Aging / Q000502:physiology; D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002817:Chordoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007403:Intervertebral Disc / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009672:Notochord / Q000166:cytology* / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013629:Tamoxifen / Q000494:pharmacology
D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D013629:Tamoxifen