Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish

Lu, Shuxian; Lyu, Zhaojie; Wang, Wenwen; Kou, Yao; Liu, Cong; Li, Shengyue; Hu, Mengyan; Zhu, Hongjie; Wang, Wenxing; Zhang, Ce; Kuan, Yi‐Chun; Liu, Yiwen; Chen, Jianming; Tian, Jing

doi:10.7150/thno.53330

Cited by 15 publications

(12 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We, herein, attempt to evaluate the mobility of different zebrafish groups, e.g., the ones with lipin-1 deficiency and anesthetized ones (Lu et al, 2021 ). Optimally, both the macroscopic fish movement and its neuron system at the single-cell level are monitored in real-time to establish direct connections.…”

Section: Resultsmentioning

confidence: 99%

“…In 2016, Suriyampola et al found that zebrafish become more aggressive and form less cohesive groups when they were transitioned from still water to a water environment of low flow rate (Sykes et al, 2018 ). However, in most studies, the behavior of zebrafish larvae was studied using the touch-evoked approach, in which a stick was used to manually poke the target zebrafish (Lu et al, 2021 ). For studies at the single cell level, e.g., the development of early neurons, zebrafish has to be anesthetized, which lacks dynamic stimuli like the continuous flow in the wild (Park et al, 2000 ; Palaisa and Granato, 2007 ; Santanu et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A fluidic platform for mobility evaluation of zebrafish with gene deficiency

Jia

Feng

et al. 2023

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

IntroductionZebrafish is a suitable animal model for molecular genetic tests and drug discovery due to its characteristics including optical transparency, genetic manipulability, genetic similarity to humans, and cost-effectiveness. Mobility of the zebrafish reflects pathological conditions leading to brain disorders, disrupted motor functions, and sensitivity to environmental challenges. However, it remains technologically challenging to quantitively assess zebrafish's mobility in a flowing environment and simultaneously monitor cellular behavior in vivo.MethodsWe herein developed a facile fluidic device using mechanical vibration to controllably generate various flow patterns in a droplet housing single zebrafish, which mimics its dynamically flowing habitats.ResultsWe observe that in the four recirculating flow patterns, there are two equilibrium stagnation positions for zebrafish constrained in the droplet, i.e., the “source” with the outward flow and the “sink” with the inward flow. Wild-type zebrafish, whose mobility remains intact, tend to swim against the flow and fight to stay at the source point. A slight deviation from streamline leads to an increased torque pushing the zebrafish further away, whereas zebrafish with motor neuron dysfunction caused by lipin-1 deficiency are forced to stay in the “sink,” where both their head and tail align with the flow direction. Deviation angle from the source point can, therefore, be used to quantify the mobility of zebrafish under flowing environmental conditions. Moreover, in a droplet of comparable size, single zebrafish can be effectively restrained for high-resolution imaging.ConclusionUsing the proposed methodology, zebrafish mobility reflecting pathological symptoms can be quantitively investigated and directly linked to cellular behavior in vivo.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A fluidic platform for mobility evaluation of zebrafish with gene deficiency

Jia

Feng

et al. 2023

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Total RNA was extracted from zebrafish embryos and mice intestinal tissues using TRIzol reagent (Ambion, Austin, TX, USA) and subjected to reverse transcription using the SuperScriptIII (Invitrogen, Carlsbad, CA, USA). qRT-PCR was carried out as described previously using SYBR FAST Universal qPCR kit (Kapa Biosystems, Boston, MA, USA), and ViiA 7 Real-Time PCR System (ABI, Foster City, CA, USA) [69]. The PCR conditions consisted of a denaturation step for 3 min at 95 • C followed by 40 cycles of 95 • C for 3 s and 60 • C for 20 s. Primer sequences are listed in Table S4.…”

Section: Rna-seq and Bioinformatic Analysismentioning

confidence: 99%

Bacterial Quorum-Sensing Signal DSF Inhibits LPS-Induced Inflammations by Suppressing Toll-like Receptor Signaling and Preventing Lysosome-Mediated Apoptosis in Zebrafish

Zhu

Wang

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Bacteria and their eukaryotic hosts have co-evolved for millions of years, and the former can intercept eukaryotic signaling systems for the successful colonization of the host. The diffusible signal factor (DSF) family represents a type of quorum-sensing signals found in diverse Gram-negative bacterial pathogens. Recent evidence shows that the DSF is involved in interkingdom communications between the bacterial pathogen and the host plant. In this study, we explored the anti-inflammatory effect of the DSF and its underlying molecular mechanism in a zebrafish model. We found that the DSF treatment exhibited a strong protective effect on the inflammatory response of zebrafish induced by lipopolysaccharide (LPS). In the LPS-induced inflammation zebrafish model, the DSF could significantly ameliorate the intestinal pathological injury, reduce abnormal migration and the aggregation of inflammatory cells, inhibit the excessive production of inflammatory mediator reactive oxygen species (ROS) content, and prevent apoptosis. Through an RNA-Seq analysis, a total of 938 differentially expressed genes (DEGs) was screened between LPS and LPS + DSF treatment zebrafish embryos. A further bioinformatics analysis and validation revealed that the DSF might inhibit the LPS-induced zebrafish inflammatory response by preventing the activation of signaling in the Toll-like receptor pathway, attenuating the expression of pro-inflammatory cytokines and chemokines, and regulating the activation of the caspase cascade through restoring the expression of lysosomal cathepsins and apoptosis signaling. This study, for the first time, demonstrates the anti-inflammatory role and a potential pharmaceutical application of the bacterial signal DSF. These findings also suggest that the interkingdom communication between DSF-producing bacteria and zebrafish might occur in nature.

show abstract

“…As a well-established animal model, the zebrafish has widely been used in the study of metabolic diseases and diabetic complications due to its unique advantages in high fecundity, short generation time, and rapid external development of transparent embryos ( Heckler and Kroll, 2017 ; Wiggenhauser and Kroll, 2019 ). Furthermore, zebrafish are also well-studied for peripheral neuropathy due to the visibility of peripheral motor neurons by using special genetic lines ( Gong et al, 2020 ; Lu et al, 2021 ). Ennerfelt et al proved that hyperglycemia disrupted peripheral nerve development in a zebrafish model, suggesting zebrafish as an emerging model for studying DPN ( Ennerfelt et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Acrolein-inducing ferroptosis contributes to impaired peripheral neurogenesis in zebrafish

Kan

Sticht

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

IntroductionDiabetes mellitus (DM) is associated with physiological disorders such as delayed wound healing, diabetic retinopathy, diabetic nephropathy, and diabetic peripheral neuropathy (DPN). Over 50% of diabetic patients will develop DPN, characterized by motor dysfunction and impaired sensory nerve function. In a previous study, we have uncovered acrolein (ACR) as an upstream initiator which induced impaired glucose homeostasis and microvascular alterations in zebrafish. Whether ACR has specific effects on peripheral neurogenesis and mediates DPN, is still waiting for clarification.MethodsTo evaluate the function of ACR in peripheral nerve development, in vivo experiments were performed in Tg(hb9:GFP) zebrafish. In addition, a series of rescue experiments, metabolomics assessment, and bioinformatics analysis was performed aimed at identifying the molecular mechanisms behind ACR’s function and impaired neurogenesis.ResultsImpaired motor neuron development was confirmed in wild-type embryos treated with external ACR. ACR treated embryos displayed ferroptosis and reduction of several amino acids and increased glutathione (GSH). Furthermore, ferroptosis inducer caused similarly suppressed neurogenesis in zebrafish embryos, while anti-ACR treatment or ferroptosis inhibitor could successfully reverse the detrimental phenotypes of ACR on neurogenesis in zebrafish.DiscussionOur data indicate that ACR could directly activate ferroptosis and impairs peripheral neurogenesis. The data strongly suggest ACR and activated ferroptosis as inducers and promising therapeutic targets for future DPN studies.

show abstract

Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish

Cited by 15 publications

References 74 publications

A fluidic platform for mobility evaluation of zebrafish with gene deficiency

A fluidic platform for mobility evaluation of zebrafish with gene deficiency

Bacterial Quorum-Sensing Signal DSF Inhibits LPS-Induced Inflammations by Suppressing Toll-like Receptor Signaling and Preventing Lysosome-Mediated Apoptosis in Zebrafish

Acrolein-inducing ferroptosis contributes to impaired peripheral neurogenesis in zebrafish

Contact Info

Product

Resources

About