PgmNr Z6168: Braciole: a novel motile cilia mutation which exhibits neural randomization and scoliosis.

Authors:
Nicholas Morante; Shin-Yi Lin; Stuart Carter; Eunice Lee; Daniel Grimes; Rebecca Burdine

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Institutes
Princeton University, Princeton, NJ.

Abstract:
Primary ciliary dyskinesia (PCD) is a relatively rare genetic condition, affecting around 1 in 10,000 people, that is caused by defects in ciliary motility. PCD patients often exhibit infertility, left-right (L-R) axis randomization, otitis media, and bronchiectasis. The involvement of motile cilia in the development of in these defects has been the focus of much research on motile cilia. However, in addition to these disorders, recent findings have unearthed new potential associations between motile cilia and diseases, notably in the etiopathogenesis of adolescent idiopathic scoliosis (AIS), highlighting the need for a close re-examination of the consequences motile cilia defects in vertebrates. Here we describe the characterization of a novel motile cilia mutant, braciole (brcl), which exhibits developmental defects associated with motile cilia abnormalities. We demonstrate that brcl encodes a novel dyx1c1 mutation that results in a loss of ciliary outer dynein arms and complete cilia immotility. We further develop a technique to allow us to rescue embryonic defects and thereby characterize later roles for motile cilia in juveniles and adults. We find that dyx1c1is required to maintain spine straightness during growth and that mutation causes three-dimensional spinal curvatures that closely model idiopathic scoliosis.