Delineating the role of the notochord during intervertebral disc development

The objective of this project is to delineate the phenotype of notochord cells at distinct stages of IVD development and assess their role as tissue-specific progenitors.  As a basis for these studies, we have characterized a novel notochord-specific Cre recombinase mouse strain generated by targeting the mouse gene encoding the notochord-specific transcription factor Noto.

The first report of this mouse to conduct fate-mapping of the notochord during spine development enabled us to establish that all cells in the murine nucleus pulposus are derived from the embryonic notochord, and not through invasion of cells from the surrounding mesenchyme (McCann et al. Dis Mod Mech).

This strategy now affords us the unique ability to isolate notochord cells at distinct stages of IVD formation to delineate the phenotype associated notochord differentiation, studies that will address a pressing need in the field by identifying cell type-specific IVD markers and identifying the pathways that regulate IVD homeostasis.