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

Cell and Developmental Biology

Kareem C. Clark¹  Manxiu Ma¹  Y. Albert Pan²  Alyssa A. Brunal³  Carleigh Studtmann³  Katelyn Stebbins⁴  Shin-ichi Higashijima⁵ 

[1] Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United States;Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United States;Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States;Department of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, United States;Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United States;Translational Biology Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, United States;Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, United States;Translational Biology Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, United States;Virginia Tech Carilion School of Medicine, Roanoke, VA, United States;National Institutes of Natural Sciences, Exploratory Research Center on Life and Living Systems, National Institute for Basic Biology, Okazaki, Aichi, Japan;

关键词: HPA (hypothalamic-pituitary-adrenal) axis;    zebrafish;    CRH neuron;    hypothalamus;    development;   

DOI  :  10.3389/fcell.2023.1113675

 received in 2022-12-01, accepted in 2023-01-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Ma, Brunal, Clark, Studtmann, Stebbins, Higashijima and Pan.