Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis

Zhang, Xiaoli; Jia, Shijie; Chen, Zhe; Chong, Yan Ling; Xie, Haibo; Dong, Feng; Wu, Xiaotong; Song, Zhu; Roy, Sudipto; Zhao, Chengtian

doi:10.1038/s41588-018-0260-3

Cited by 118 publications

(249 citation statements)

References 32 publications

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“…To verify that asymmetric cilia beating is solely responsible for the bidirectional flow i n vivo , we injected beads in the diencephalic ventricle of several mutants for which either ciliogenesis or ciliary motility is affected. Consistently with previous reports 36,39 , longrange transport of beads down the central canal is altered in mutants with defective cilia ( Figure 4a1, 4a2 ). In paralyzed mutant embryos several hours post injection, no particles entered the CC, as shown here in traf3ip tp49d/tp49 , commonly referred to as elipsa 44 .…”

Section: Cilia Activity Controls Csf Longrange Transport CC Structursupporting

confidence: 93%

“…We report that mutants with defective cilia were Figure 3c ), since a few cilia remain motile in kurly embryos 54 and in elipsa between 24 hpf and 30 hpf 39 . The model also accounts for the reduced longrange transport previously observed in kif3b mutants, where cilia density is reduced 36 . In contrast, foxj1a mutant embryos showing ependymal cells with defective cilia 55 ( Supplementary Figure S3 ) have a completely collapsed CC.…”

Section: Discussionmentioning

confidence: 98%

“…Now that the CSF flow has been fully characterized, its ability to transport particles on long distances needs to be demonstrated. The longrange transport follows an apparent diffusive law, as the propagation front of nanoparticles progresses with the square root of time 36 and depends on particle size ( Figure 6a1, 6a2 ). The propagation front is also accelerated by muscle contractions ( Figure 6a3 ).…”

Section: Bidirectional Longrange Transport In the Central Canal Is Acmentioning

confidence: 99%

“…The CSF provides the hydromechanical protection of the brain 25 , enables the transport of nutrients and waste 25,26 , exosomes [27][28][29][30][31] , and signaling molecules impacting neurogenesis and neuronal migration in the brain [32][33][34][35] . The CSF circulation has recently been linked to body axis formation in the embryo and spine morphogenesis in juveniles/adults 21,36,37 . During embryogenesis, mutations affecting ciliogenesis, cilia polarity or motility lead to defects of transport along the rostrocaudal axis and body axis formation 36,38 .…”

Section: Introductionmentioning

confidence: 99%

“…The CSF circulation has recently been linked to body axis formation in the embryo and spine morphogenesis in juveniles/adults 21,36,37 . During embryogenesis, mutations affecting ciliogenesis, cilia polarity or motility lead to defects of transport along the rostrocaudal axis and body axis formation 36,38 .…”

Section: Introductionmentioning

confidence: 99%

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Origin of the bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Thouvenin

Keiser

Cantaut-Belarif

et al. 2019

Preprint

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The circulation of cerebrospinal fluid (CSF) plays pivotal roles for body axis formation and brain development. During embryogenesis, CSF is rich in particles and proteins and flows bidirectionally in the central canal. The origins of bidirectional flow and its impact on development are unknown. Experiments combined with modeling and simulations demonstrate that the bidirectionality of CSF flow is generated locally by caudallypolarized motile cilia confined to the ventral wall of the central canal. Such active bidirectional flow of the CSF accelerates the longrange transport of particles propagating rostrally and caudally. In addition, spontaneous muscle contractions increase local CSF flow and consequently enhance longrange transport of extracellular lipidic particles. Focal ablation of the channel connecting brain ventricles to the central canal reduces embryo length, indicating that longrange transport contributes to embryonic growth. Our study also demonstrates that at this early stage, motile cilia ensure the proper formation of the central canal.

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Section: Cilia Activity Controls Csf Longrange Transport CC Structursupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Bidirectional Longrange Transport In the Central Canal Is Acmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Origin of the bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Thouvenin

Keiser

Cantaut-Belarif

et al. 2019

Preprint

View full text Add to dashboard Cite

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Teratogenic and Neurotoxic Effects of n‐Butanol on Zebrafish Development

et al. 2021

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In recent years, n‐butanol, a type of alcohol, has been widely used from the chemical industry to the food industry. In this study, toxic effects of n‐butanol's different concentrations (10, 50, 250, 500, 750, 1,000, and 1,250 mg/L) in Zebrafish Danio rerio embryos and larvae were investigated. For this purpose, Zebrafish embryos were exposed to n‐butanol in acute semistatic applications. Teratogenic effects such as cardiac edema, scoliosis, lordosis, head development abnormality, yolk sac edema, and tail abnormality were determined at different time intervals (24, 48, 72, 96, and 120 h). Additionally, histopathological abnormalities such as vacuole formation in brain tissue and necrosis in liver tissue were observed at high doses (500, 750, and 1,000 mg/L) in all treatment groups at 96 h. It was determined that heart rate decreased at 48, 72, and 96 h due to an increase in concentration. In addition, alcohol‐induced eye size reduction (microphthalmia) and single eye formation (cyclopia) are also among the effects observed in our research findings. In conclusion, n‐butanol has been observed to cause intense neurotoxic, teratogenic, and cardiotoxic effects in Zebrafish embryos and larvae.

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Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish

et al. 2021

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Idiopathic scoliosis (IS) is a spinal disorder affecting up to 3% of otherwise healthy children. IS has a strong familial genetic component and is believed to be genetically complex due to significant variability in phenotype and heritability. Previous studies identified putative loci and variants possibly contributing to IS susceptibility, including within extracellular matrix, cilia, and actin networks, but the genetic architecture and underlying mechanisms remain unresolved. Here, we used whole‐exome sequencing from three affected individuals in a multigenerational family with IS and identified 19 uncommon variants (minor allele frequency < 0.05). Genotyping of additional family members identified a candidate heterozygous variant (H1115Q, G>C, rs142032413) within the ciliary gene KIF7, a regulator within the hedgehog (Hh) signaling pathway. Resequencing of the second cohort of unrelated IS individuals and controls identified several severe mutations in KIF7 in affected individuals only. Subsequently, we generated a mutant zebrafish model of kif7 using CRISPR‐Cas9. kif7co63/co63 zebrafish displayed severe scoliosis, presenting in juveniles and progressing through adulthood. We observed no deformities in the brain, Reissner fiber, or central canal cilia in kif7co63/co63 embryos, although alterations were seen in Hh pathway gene expression. This study suggests defects in KIF7‐dependent Hh signaling, which may drive pathogenesis in a subset of individuals with IS.

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Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis

Cited by 118 publications

References 32 publications

Origin of the bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Origin of the bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Teratogenic and Neurotoxic Effects of n‐Butanol on Zebrafish Development

Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish

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