Serotoninergic Regulation of Body Axis Morphology

Idiopatic scoliosis (IS) is a human pathology that affects 1-4% of adolescents worldwide, who suffer from spine deformities for which an effective treatment is not currently available. At present, evidence for genetic causes of IS exist, but the aetiology of this pathology is still not understood.

The zebrafish is a powerful organism to model human pathologies that entail body axis misalignment as, by swimming in a viscous liquid, its spine is subject to forces similar to the ones acting on the spine in bipedal position. One essential player in the establishment of embryonic zebrafish longitudinal axis is the Reissner Fibre (RF).

The RF consists of SCO-spondin protein, which, during post embryonic life, is secreted by a paraventricular organ, the SCO. Zebrafish scospondin mutants lack the RF and exhibit severe scoliotic phenotype. Remarkably, a similar scoliotic phenotype is observed in the tph2-/- zebrafish, genetically depleted of serotonin.

Preliminary observations have shown that serotoninergic projections reach the SCO, in mammals and in the zebrafish.

My research objective is to unravel how the neuronal activity of serotoninergic neurons can control the maintenance of a straight longitudinal body axis during the zebrafish post embryonic life.

Firstly, a detailed characterisation of spine alignment in correlation to RF assembly will be carried out in the tph2-/- zebrafish. Secondly, the serotoninergic neurons projecting to the SCO will be anatomically located and mapped.

Thirdly, the neuronal mechanism by which serotoninergic neurons regulate RF maintenance will be functionally investigated.

The long-term goal of this research project is to gain insights in the progression of IS, and to inform preclinical research on the development of diagnostic tools, which are currently lacking.