The Requirement of Sox2 for the Spinal Cord Motor Neuron Development of Zebrafish

Gong, Jie; Hu, Songqun; Huang, Zigang; Hu, Yuebo; Wang, Xiaoning; Zhao, Jianya; Qian, Peipei; Wang, Cheng; Sheng, Jiajing; Lu, Xiaofeng; Wei, Guanyun; Liu, Dong

doi:10.3389/fnmol.2020.00034

Cited by 19 publications

(19 citation statements)

References 43 publications

(60 reference statements)

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“…To analyze the development of motor neurons, we used the transgenic line Tg(mnx1:GFP) in which GFP was driven by the motor-neuron specific transcription factor mnx1 . At 48 hpf when many motor neurons have been actively generated, most motor neurons in myt1 mutant had round cell bodies and lacked processes, which was considered as undifferentiated states (Gong, Hu, Huang, Hu, Wang, Zhao, Qian, Wang, Sheng, Lu, Wei, and Liu 2020) (Figure 6E). In zebrafish, three primary motor neurons exist in the spinal cord: caudal primary motor neurons (CaP MNs), middle primary motor neurons (MiP MNs), and rostral primary motor neurons (RoP MNs), which innervate the ventral trunk musculature, dorsal trunk musculature, and muscle fibers in between, respectively.…”

Section: Resultsmentioning

confidence: 99%

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

Xing

Chai

Wang

et al. 2021

Preprint

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The pMN domain is a restricted domain in the ventral spinal cords, defined by the expression of olig2 gene. The fate determination of pMN progenitors is highly temporally and spatially regulated, with motor neurons and oligodendrocyte progenitor cells (OPCs) developing sequentially. Insight into the heterogeneity and molecular programs of pMN progenitors is currently lacking. With the zebrafish model, we identified multiple states of neural progenitors using single-cell sequencing: proliferating progenitors, common progenitors for both motor neurons and OPCs, and restricted precursors for either motor neurons or OPCs. We found specific molecular programs for neural progenitor fate transition, and manipulations of representative genes in the motor neuron or OPC lineage confirmed their critical role in cell fate determination. The transcription factor NPAS3 is necessary for the development of the OPC lineage and can interact with many known genes associated with schizophrenia. Deciphering progenitor heterogeneity and molecular mechanisms for these transitions will elucidate the formation of complex neuron-glia networks in the central nervous system during development, and understand the basis of neurodevelopmental disorders.

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Section: Resultsmentioning

confidence: 99%

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

Xing

Chai

Wang

et al. 2021

Preprint

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“…Zebrafish embryos and adults were maintained in at the Zebrafish Center of Nantong University in accordance with guidelines outlined in previous studies ( Xu et al, 2014 ; Gong et al, 2017 , 2020 ). The transgenic zebrafish line, Tg(mnx1:GFP)ml2 and Tg(kdrl:EGFP) line have been described in the previous work ( Flanagan-Steet et al, 2005 ; Jin et al, 2005 ).…”

Section: Methodsmentioning

confidence: 99%

“…They were then dehydrated through a series of increasing methanol concentrations, and finally stored in 100% methanol at −20°C. WISH was performed as previously described ( Gong et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…In our previous studies, we reported that insm1a, kinesin-12, and sox2 had key roles in motor neuron development ( Xu et al, 2014 ; Gong et al, 2017 , 2020 ). For example, the zebrafish insm1a mutant showed motor neuron loss and defects in PMN axons, including truncated length, excessive Cap branches, and disorganized distances between adjacent Caps, which were caused by the ectopic departure of motor axons from the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

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Nexmifa Regulates Axon Morphogenesis in Motor Neurons in Zebrafish

Zheng

Suo

Liu

et al. 2022

Front. Mol. Neurosci.

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Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.

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“…The zebrafish embryos and adults were maintained in the zebrafish Center of Nantong University under conditions following our previous protocols ( Gong et al, 2020 ). Wild-type (AB) control and Tg(Brn3c:GFP) transgenic zebrafish whose hair cells were labeled by GFP were used in this study ( Xiao et al, 2005 ).…”

Section: Methodsmentioning

confidence: 99%

Claudin h Is Essential for Hair Cell Morphogenesis and Auditory Function in Zebrafish

Gong

Qian

et al. 2021

Front. Cell Dev. Biol.

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Hereditary hearing loss caused by defective hair cells is one of the most common congenital diseases, whose nosogenesis is still unclear because many of the causative genes remain unidentified. Claudins are one kind of transmembrane proteins that constitute the most important components of the tight junctions and paracellular barrier and play important roles in neurodevelopment. In this study, we investigated the function of claudin h in morphogenesis and auditory function of the hair cell in zebrafish. The results of in situ hybridization showed that claudin h was specifically localized in the otic vesicle and neuromasts in zebrafish embryos. The deficiency of claudin h caused significant reduction of otic vesicle size and loss of utricle otolith. Moreover, the startle response and vestibulo-ocular reflex experiments revealed that loss of claudin h led to serious hearing loss and vestibular dysfunction. Importantly, the confocal microscopy observation found that compared to the control zebrafish, the claudin h morphants and mutants displayed significantly reduced the number of cristae hair cells and shortened kinocilia. Besides, the deficiency of claudin h also caused the loss of hair cells in neuromasts which could be rescued by injecting claudin h mRNA into the mutant embryos at one cell stage. Furthermore, the immunohistochemistry experiments demonstrated remarkable apoptosis of hair cells in the neuromasts, which might contribute to the loss of hair cells number. Overall, these data indicated that claudin h is indispensable for the development of hair cells, vestibular function, and hearing ability of zebrafish.

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The Requirement of Sox2 for the Spinal Cord Motor Neuron Development of Zebrafish

Cited by 19 publications

References 43 publications

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

Nexmifa Regulates Axon Morphogenesis in Motor Neurons in Zebrafish

Claudin h Is Essential for Hair Cell Morphogenesis and Auditory Function in Zebrafish

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