PUBLICATION
Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis
- Authors
- Zhang, X., Jia, S., Chen, Z., Chong, Y.L., Xie, H., Feng, D., Wu, X., Song, D.Z., Roy, S., Zhao, C.
- ID
- ZDB-PUB-181114-25
- Date
- 2018
- Source
- Nature Genetics 50(12): 1666-1673 (Journal)
- Registered Authors
- Roy, Sudipto, Zhao, Chengtian
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Body Patterning
- Cerebrospinal Fluid/physiology*
- Cilia/physiology*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Morphogenesis/physiology
- Neuropeptides/genetics
- Signal Transduction/genetics
- Spinal Cord/embryology
- Urotensins/genetics*
- Vertebrates/embryology
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 30420648 Full text @ Nat. Genet.
Citation
Zhang, X., Jia, S., Chen, Z., Chong, Y.L., Xie, H., Feng, D., Wu, X., Song, D.Z., Roy, S., Zhao, C. (2018) Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis. Nature Genetics. 50(12):1666-1673.
Abstract
Straightening of the body axis is a major morphogenetic event that produces the typical head-to-tail shape of the vertebrate embryo. Defects in axial straightening can lead to debilitating disorders such as idiopathic scoliosis, characterized by three-dimensional curvatures of the spine1. Although abnormal cerebrospinal fluid (CSF) flow has been implicated in the development of idiopathic scoliosis2, the molecular mechanisms operating downstream of CSF flow remain obscure. Here we show that, in zebrafish embryos, cilia-driven CSF flow transports adrenergic signals that induce urotensin neuropeptides in CSF-contacting neurons along the spinal cord. Urotensins activate their receptor on slow-twitch muscle fibers of the dorsal somite; the contraction of these fibers likely results in straightening of the body axis. Consistent with this, mutation of the urotensin receptor resulted in severe scoliosis in adult zebrafish, closely mimicking the human disorder. These findings suggest that disruption of urotensin signaling by impaired CSF flow could be a critical etiological factor underlying the pathology of idiopathic scoliosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping