Foxj1a is expressed in ependymal precursors, controls central canal position and is activated in new ependymal cells during regeneration in zebrafish

Ribeiro, Ana; Monteiro, Joana F.; Certal, Ana C.; Cristóvão, Ana Margarida; Saúde, Leonor

doi:10.1098/rsob.170139

Cited by 31 publications

(24 citation statements)

References 54 publications

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“…To build a theoretical model of CSF flow, we quantify essential parameters such as the canal geometry and the local cilia dynamics. The central canal geometry, as estimated by Dextran injections, corresponds to a cylinder ( Figure 2a1, 2a2 ) of diameter 8.9 ± 0.9 μm (129 WT embryos, Figure 2a3 ) with a very small dorsal extension showing low fluorescence level in the uppermost position, as previously observed with antibody staining for tightjunctions 41 . The dynamics of motile cilia in the CC are investigated in 30 hpf Tg(βactin:Arl13bGFP) embryos in which GFP labels all cilia 31,39,42 .…”

Section: Central Canal Geometry and Properties Of The Motile Ciliasupporting

confidence: 70%

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: Central Canal Geometry and Properties Of The Motile Ciliasupporting

confidence: 70%

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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“…We have identified two different subpopulations of motile ciliated cells based on the expression pattern of the two Foxj1 orthologs and the analysis of ciliary mutants. Our results obtained with a 0.6kbfoxj1a:gfp and 5.2kbfoxj1a:gfp [ 17 ] transgenic lines demonstrated that these promoter regions are not sufficient to drive the specific expression pattern of foxj1a in the larval brain and suggest that other regulatory elements may be involved in its transcriptional regulation [ 57 ]. Nevertheless, our data revealed that both foxj1a - and foxj1b -positive cells are needed to generate a robust CSF flow in the ventricles.…”

Section: Discussionmentioning

confidence: 99%

Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

Olstad

Ringers

Hansen³

et al. 2019

Current Biology

167

194

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SummaryMotile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.

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“…Moreover, the ratio of highly expressing CSF-cNs (full arrowheads) was significantly increased in scoliotic (but more variably in straight) rpgrip1l ∆/∆ fish. To determine whether increased expression of URP1/2 peptides can trigger scoliosis, we injected a transgenic construct expressing urp2 in foxj1+ cells, lining central nervous system cavities [27], in eggs from rpgrip1l ∆/+ crosses.…”

Section: Upregulation Of Urp Signaling Participates In Scoliosis Onsementioning

confidence: 99%

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

Vesque

Anselme

Pézeron³

et al. 2019

Preprint

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Cilia-driven movements of the cerebrospinal fluid (CSF) are involved in zebrafish axis straightness, both in embryos and juveniles [1,2]. In embryos, axis straightness requires ciliadependent assembly of the Reissner fiber (RF), a SCO-spondin polymer running down the brain and spinal cord CSF-filled cavities [3]. Reduced expression levels of the urp1 and urp2 genes encoding neuropeptides of the Urotensin II family in CSF-contacting neurons (CSF-cNs) also underlie embryonic ventral curvature of several cilia motility mutants [4]. Moreover, mutants for scospondin and uts2r3 (a Urotensin II peptide family receptor gene) develop scoliosis at juvenile stages [3,4]. However, whether RF maintenance and URP signaling are perturbed in juvenile scoliotic ciliary mutants and how these perturbations are linked to scoliosis is unknown. Here we produced mutants in the zebrafish ortholog of the human RPGRIP1L ciliopathy gene encoding a transition zone protein [5][6][7]. rpgrip1l -/zebrafish had normal embryogenesis and developed 3D spine torsions in juveniles. Cilia lining the CNS cavities were normal in rpgrip1l -/embryos but sparse and malformed in juveniles and adults.Hindbrain ventricle dilations were present at scoliosis onset, suggesting defects in CSF flow.Immunostaining showed a secondary loss of RF correlating with juvenile scoliosis.Surprisingly, transcriptome analysis of rgprip1l mutants at scoliosis onset uncovered increased levels of urp1 and urp2 expression. Overexpressing urp2 in foxj1-expressing cells triggered scoliosis in rpgrip1l heterozygotes. Thus, our results demonstrate that increased URP signaling drives scoliosis onset in a ciliopathy mutant. We propose that imbalanced levels of URP neuropeptides in CSF-cNs may be an initial trigger of scoliosis.

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Foxj1a is expressed in ependymal precursors, controls central canal position and is activated in new ependymal cells during regeneration in zebrafish

Cited by 31 publications

References 54 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

Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

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