PgmNr Z636: Linking cilia motility and cerebrospinal fluid flow to the etiopathogenesis of adolescent idiopathic scoliosis.

Authors:
D. T. Grimes 1 ; C. Boswell 2 ; N. F. C. Morante 1 ; R. M. Henkelman 2 ; R. D. Burdine 1 ; B. Ciruna 2


Institutes
1) Princeton University, Princeton, NJ; 2) Hospital for Sick Children, University of Toronto, Canada.


Abstract:

Adolescent idiopathic scoliosis (AIS), a disease characterized by 3D spinal curvatures, afflicts 2-3% of children worldwide. However, the underlying biological basis for this disease has remained unknown. Recently, the teleost fish have emerged as robust models of AIS. Using zebrafish, we have discovered that spinal curves are caused by loss of motile cilia function, which in turn results in defective CSF flow. Human AIS can be caused by mutations in PTK7, and we find that cilia/CSF flow defects are also the basis of spinal curves in ptk7 zebrafish mutants. Thus, we propose that AIS can be caused by disruptions to CSF flow, providing a novel mechanism for this prevalent disease. We also provide evidence that spinal curves can be partially rescued by restoring cilia motility after curve onset, opening potential therapeutic avenues.



ZFIN Genetics Index
1. ptk7