Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism
The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3459 |
| _version_ | 1797240681113059328 |
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| author | Qiang Gu Jyotshna Kanungo |
| author_facet | Qiang Gu Jyotshna Kanungo |
| author_sort | Qiang Gu |
| collection | DOAJ |
| description | The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism. |
| first_indexed | 2024-04-24T18:11:17Z |
| format | Article |
| id | doaj.art-58678eb168284c559d97aef88b1174fa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:11:17Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58678eb168284c559d97aef88b1174fa2024-03-27T13:46:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256345910.3390/ijms25063459Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling AutismQiang Gu0Jyotshna Kanungo1Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USADivision of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USAThe exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism.https://www.mdpi.com/1422-0067/25/6/3459arseniczebrafishSonic hedgehogautismmotor neuron |
| spellingShingle | Qiang Gu Jyotshna Kanungo Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism International Journal of Molecular Sciences arsenic zebrafish Sonic hedgehog autism motor neuron |
| title | Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism |
| title_full | Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism |
| title_fullStr | Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism |
| title_full_unstemmed | Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism |
| title_short | Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism |
| title_sort | neurogenic effects of inorganic arsenic and cdk5 knockdown in zebrafish embryos a perspective on modeling autism |
| topic | arsenic zebrafish Sonic hedgehog autism motor neuron |
| url | https://www.mdpi.com/1422-0067/25/6/3459 |
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