Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function
The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1113675/full |
| _version_ | 1797905034312155136 |
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| author | Manxiu Ma Alyssa A. Brunal Alyssa A. Brunal Kareem C. Clark Carleigh Studtmann Carleigh Studtmann Katelyn Stebbins Katelyn Stebbins Katelyn Stebbins Shin-ichi Higashijima Y. Albert Pan Y. Albert Pan Y. Albert Pan |
| author_facet | Manxiu Ma Alyssa A. Brunal Alyssa A. Brunal Kareem C. Clark Carleigh Studtmann Carleigh Studtmann Katelyn Stebbins Katelyn Stebbins Katelyn Stebbins Shin-ichi Higashijima Y. Albert Pan Y. Albert Pan Y. Albert Pan |
| author_sort | Manxiu Ma |
| collection | DOAJ |
| description | The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in zebrafish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1-linked neuropsychiatric disorders. |
| first_indexed | 2024-04-10T09:58:40Z |
| format | Article |
| id | doaj.art-37c15cf49b12424884b55d2b28283cde |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T09:58:40Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-37c15cf49b12424884b55d2b28283cde2023-02-16T10:23:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.11136751113675Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis functionManxiu Ma0Alyssa A. Brunal1Alyssa A. Brunal2Kareem C. Clark3Carleigh Studtmann4Carleigh Studtmann5Katelyn Stebbins6Katelyn Stebbins7Katelyn Stebbins8Shin-ichi Higashijima9Y. Albert Pan10Y. Albert Pan11Y. Albert Pan12Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesFralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesTranslational Biology Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, United StatesFralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesFralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesTranslational Biology Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, United StatesFralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesTranslational Biology Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, United StatesVirginia Tech Carilion School of Medicine, Roanoke, VA, United StatesNational Institutes of Natural Sciences, Exploratory Research Center on Life and Living Systems, National Institute for Basic Biology, Okazaki, Aichi, JapanFralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United StatesDepartment of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, United StatesThe corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in zebrafish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1-linked neuropsychiatric disorders.https://www.frontiersin.org/articles/10.3389/fcell.2023.1113675/fullHPA (hypothalamic-pituitary-adrenal) axiszebrafishCRH neuronhypothalamusdevelopment |
| spellingShingle | Manxiu Ma Alyssa A. Brunal Alyssa A. Brunal Kareem C. Clark Carleigh Studtmann Carleigh Studtmann Katelyn Stebbins Katelyn Stebbins Katelyn Stebbins Shin-ichi Higashijima Y. Albert Pan Y. Albert Pan Y. Albert Pan Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function Frontiers in Cell and Developmental Biology HPA (hypothalamic-pituitary-adrenal) axis zebrafish CRH neuron hypothalamus development |
| title | Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function |
| title_full | Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function |
| title_fullStr | Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function |
| title_full_unstemmed | Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function |
| title_short | Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function |
| title_sort | deficiency in the cell adhesion molecule dscaml1 impairs hypothalamic crh neuron development and perturbs normal neuroendocrine stress axis function |
| topic | HPA (hypothalamic-pituitary-adrenal) axis zebrafish CRH neuron hypothalamus development |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1113675/full |
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