Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
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Query: UMLS:C0700208 (
scoliosis
)
8,574
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Reissner fibre (RF), discovered by the 19
th
-century German anatomist Ernst Reissner, is a filamentous structure present in cerebrospinal fluid (CSF). RF forms by aggregation of a glycoprotein called
SCO-spondin
(Sspo), but its function has remained enigmatic. Recent studies have shown that zebrafish
sspo
mutants develop a curved embryonic body axis. Zebrafish embryos with impaired cilia motility also develop curved bodies, which arises from failure of expression of
urotensin related peptide
(
urp
) genes in CSF-contacting neurons (CSF-cNs), impairing downstream signalling in trunk muscles. Here, we show that
sspo
mutants can survive into adulthood, but display severe curvatures of the vertebral column, resembling the common human spine disorder idiopathic
scoliosis
(IS).
sspo
mutants also exhibit significant reduction of
urp
gene expression from CSF-cNs. Consistent with epinephrine in CSF being bound by RF and required for
urp
expression, treating
sspo
mutants with this catecholamine rescued expression of the
urp
genes and axial defects. More strikingly, providing Urp2, specifically in the CSF-cNs, rescued body curvature of
sspo
homozygotes during larval stages as well as in the adult. These findings bridge existing gaps in our knowledge between cilia motility, RF, Urp signalling and spine deformities, and suggest that targeting the Urotensin pathway could provide novel therapeutic avenues for IS.
...
PMID:Reissner fibre-induced urotensin signalling from cerebrospinal fluid-contacting neurons prevents scoliosis of the vertebrate spine. 3240 96
