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    Home > Active Ingredient News > Study of Nervous System > NgAgo is completely useless of scientific research value?

    NgAgo is completely useless of scientific research value?

    • Last Update: 2021-12-05
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    iNature cadherins play an important role in tissue homeostasis because they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation
    .

    On November 8, 2021, Liu Yan and Guan Tuchen of Nantong University published a research paper entitled "Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons" in Frontiers in Cell and Developmental Biology.
    The clinical significance of CDH12 (encoding type II classical cadherin) in axon extension is determined and introduced, and PKA signaling is an important pathway responsible for the inhibition of siCDH12-induced cytoskeletal remodeling regulator Rac1/Cdc42
    .

    First, the study evaluated the effect of CDH12 on neurons through RNA interference, and the results showed that knockdown of CDH12 expression inhibited the axon extension of E18 neurons
    .

    The transcriptome profile of neurons treated with or without siCDH12 reveals a set of pathways that are positively correlated with the effect of CDH12 on neurite outgrowth
    .

    The study further revealed that after testing with H-89 and 8-bromo-cAMP sodium salt, CDH12 affects Rac1/Cdc42 phosphorylation in a PKA-dependent manner
    .

    In addition, the study used immunofluorescence staining to study the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development
    .

    Later, the study explored the effect of CDH12 on the growth of neurites in the body
    .

    A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the important role of CDH12 in peripheral neurogenesis was determined
    .

    In conclusion, this study reported for the first time the effect of CDH12 on axon extension in vitro and in vivo, and provided a preliminary explanation for the mechanism
    .

    Vulnerability is one of the distinctive features of neuron axons, and it is the basic way to communicate with other neurons
    .

    Damage to any position along the length of the axon will result in the silence of its function
    .

    Much effort has been made to study the cellular and molecular mechanisms that regulate axon growth and regeneration
    .

    Most of the central nervous system (CNS) neurons have poor inhibitory environment and poor intrinsic growth ability, which leads to adult regeneration failure and insufficient functional recovery
    .

    The limited ability of neuron regeneration has always been the focus of research in this field
    .

    The regenerative capacity of neurons varies with developmental stages, organs, and species
    .

    In previous studies, an in vitro model was established, which showed the ability of axon extension according to different developmental stages to retrieve key molecules that lead to differences in regenerative ability
    .

    RNA-Seq analysis was also performed to collect genes whose expression continued to decline during development
    .

    Since calcium-dependent membrane proteins are involved in cell adhesion and recognition, cadherins constitute a large superfamily with more than 100 members in humans
    .

    They can be divided into several sub-families based on sequence similarity, such as classical cadherin (type I and type II) and pro-cadherin (aggregated and non-aggregated)
    .

    Cadherin plays an important role in cell sorting and tissue formation during development
    .

    Similarly, cadherin plays an important role in many stages of neural crest formation, spinal cord neurogenesis, and brain development
    .

    The processes of neurogenesis, migration, axon guidance, and synapse formation must be coordinated to ensure proper connection of neural circuits
    .

    The cadherin superfamily of cell adhesion molecules is involved in most of these events
    .

    Cadherin also acts as a receptor for signal molecules by capturing signals from the extracellular space or neighboring cells
    .

    They are also involved in regulating cell proliferation, apoptosis and differentiation
    .

    CDH12 (also known as brain cadherin) is a subtype of neurocadherin first found in the brain
    .

    Later, it was discovered that CDH12 is ubiquitously expressed in a variety of cells
    .

    Studies have confirmed that CDH12 is essential for the progression of a variety of cancers, such as salivary adenoid cystic carcinoma, colorectal cancer, and non-small cell lung cancer
    .

    In addition, CDH12 is related to some neuropsychiatric diseases
    .

    However, the role of CDH12 in neurite outgrowth is still poorly understood
    .

    On May 3, 2016, Han Chunyu’s team published a research paper entitled "DNA-guided genome editing using the Natronobacterium gregoryi Argonaute" online in Nature Biotechnology.
    The study found that Natronobacterium gregoryi Argonaute (NgAgo) is a DNA-guided nucleic acid.
    Dicer is suitable for genome editing of human cells.
    This quickly made NgAgo popular all over the world, and a large number of researchers have to verify its effect.
    Unfortunately, no relevant team can be sure that NgAgo has the function of gene editing
    .

    This led to widespread doubts.
    On August 3, 2017, Han Chunyu withdrew the paper
    .

    However, other teams have other findings.
    The Liu Dong team of Nantong University published a research paper titled "NgAgo-based fabp11a gene knockdown causes eye developmental defects in zebrafish" in Cell Research.
    The study found that gDNA / NgAgo can bind to target genes.
    Blocking its transcription, and the study did not find that NgAgo has the ability to edit genes
    .

    In this study, the clinical significance of CDH12 in axon extension was introduced, and PKA signal transduction was proposed as an important pathway responsible for the inhibition of siCDH12-induced cytoskeletal remodeling regulator Rac1/Cdc42
    .

    In addition, the expression and localization of CDH12 in the nervous system were also studied
    .

    In addition, the study performed NgAgo (a new Ago protein from Natronobacterium gregoryi)-mediated CDH12 knockdown in zebrafish for functional verification in vivo
    .

     A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system (picture from Frontiers in Cell and Developmental Biology).
    First, the study evaluated the effect of CDH12 on neurons by RNA interference, and the results showed that knockdown of CDH12 expression inhibited E18 The axon of a neuron extends
    .

    The transcriptome profile of neurons treated with or without siCDH12 reveals a set of pathways that are positively correlated with the effect of CDH12 on neurite outgrowth
    .

    The study further revealed that after testing with H-89 and 8-bromo-cAMP sodium salt, CDH12 affects Rac1/Cdc42 phosphorylation in a PKA-dependent manner
    .

    In addition, the study used immunofluorescence staining to study the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development
    .

    Later, the study explored the effect of CDH12 on the growth of neurites in the body
    .

    A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the important role of CDH12 in peripheral neurogenesis was determined
    .

    In conclusion, this study reported for the first time the effect of CDH12 on axon extension in vitro and in vivo, and provided a preliminary explanation for the mechanism
    .

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