Potential involvement of <i>DSCAML1</i> mutations in neurodevelopmental disorders

Ogata, S.; Hashizume, Koichi; Hayase, Yoneko; Kanno, Yukie; Hori, Kei; Balan, Shabeesh; Yoshikawa, Takeo; Takahashi, Hidehiko; Taya, Shinichiro; Hoshino, Mikio

doi:10.1111/gtc.12831

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…Using zebrafish as a vertebrate model for the ontogenesis of the stress axis, we found that dscaml1 deficiency results in CRH neuron deficits and dysfunction of the stress axis. Genetic perturbations of DSCAML1 are seen in patients suffering from a wide range of mental health disorders, including intellectual disability, autism spectrum disorder, schizophrenia, epilepsy, and stress disorder ( Iossifov et al, 2014 ; Caramillo et al, 2015 ; Karaca et al, 2015 ; Hayase et al, 2020 ; Ogata et al, 2021 ; Saadatmand et al, 2021 ). Developmental deficits in the stress axis may contribute to the etiology of these disorders.…”

Section: Discussionmentioning

confidence: 99%

“…DSCAML1 also acts to refine synaptic specificity and synapse number ( Yamagata and Sanes, 2008 ; Sachse et al, 2019 ). In humans, rare variants in DSCAML1 are associated with several neurodevelopmental disorders, including autism spectrum disorder, cortical abnormality, and epilepsy ( Iossifov et al, 2014 ; Karaca et al, 2015 ; Hayase et al, 2020 ; Ogata et al, 2021 ). Genetic and epigenetic studies also implicate DSCAML1 in the stress response to violent experiences ( Caramillo et al, 2015 ; Saadatmand et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Brunal

Clark

et al. 2023

Front. Cell Dev. Biol.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Brunal

Clark

et al. 2023

Front. Cell Dev. Biol.

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“…Referring to the relevant literature, some genes have affected both neural and reproductive development in animals. For instance, it has been reported that DSCAML1 affects both neural development and reproductive traits in animals ( 44 , 45 ). At the same time, growth traits and reproductive traits are inextricably linked.…”

Section: Discussionmentioning

confidence: 99%

Goat SNX29: mRNA expression, InDel and CNV detection, and their associations with litter size

Wang

et al. 2022

Front. Vet. Sci.

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The sorting nexin 29 (SNX29) gene, a member of the SNX family, is associated with material transport and lipid metabolism. Previous studies have shown that lipid metabolism affects reproductive function in animals. Thus, we hypothesized there is a correlation between the SNX29 gene and reproductive trait. To date, studies on the relationship between the SNX29 gene and reproductive traits are limited. Therefore, the purpose of this study was to examine the polymorphism in the SNX29 gene and its correlation with litter size. Herein, the mRNA expression levels of SNX29 were assayed in various goat tissue. Surprisingly, we found that SNX29 was highly expressed in the corpus luteum, large and small follicles. This result led us to suggest that the SNX29 gene has a critical role in reproduction. We further detected potential polymorphisms in Shaanbei white cashmere (SBWC) goats, including insertion/deletion (InDel, n = 2,057) and copy number variation (CNV, n = 1,402), which were related to fertility. The 17 bp deletion (n = 1004) and the 20 bp deletion (n = 1,053) within the SNX29 gene were discovered to be significantly associated with litter size (P < 0.05), and individuals the ID genotype of P1-Del-17 bp and the DD genotype of P2-Del-20bp had larger litter size. Additionally, the four CNV loci had significant correlations with litter size (P < 0.01) in our detected population. In CNV5, individuals with the median genotype were superior compared to those with loss or gain genotype in term of litter size, and in other three CNVs showed better reproductive trait in the gain genotype. Briefly, these findings suggest that SNX29 could be used as a candidate gene for litter size in goat breeding through marker-assisted selection (MAS).

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“…Using zebrafish as a vertebrate model for the ontogenesis of the stress axis, we found that dscaml1 deficiency results in CRH neuron deficits and the hyperactivation of the stress axis. Genetic perturbations of DSCAML1 are seen in patients suffering from a wide range of mental health disorders, including intellectual disability, autism spectrum disorder, schizophrenia, epilepsy, and stress disorder (Iossifov et al, 2014; Caramillo et al, 2015; Karaca et al, 2015; Hayase et al, 2020; Ogata et al, 2021; Saadatmand et al, 2021). Developmental deficits in the stress axis may contribute to the etiology of these disorders.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted September 23, 2022. ; https://doi.org/10.1101/2022.09.22.509087 doi: bioRxiv preprint Karaca et al, 2015;Hayase et al, 2020;Ogata et al, 2021). Genetic and epigenetic studies also implicate DSCAML1 in the stress response to violent experiences (Caramillo et al, 2015;Saadatmand et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the cell-adhesion moleculedscaml1impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Brunal

Clark

et al. 2022

Preprint

View full text Add to dashboard Cite

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 dysfunction and mental health disorders, it is critical to identify the molecular 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 stress axis function. In dscaml1 mutant animals, CRH neurons had higher stress axis-associated neuropeptide (crhb and avp) expression, increased cell number, decreased apoptosis, and reduced intercellular spacing as compared to controls. Time-lapse imaging showed that CRH neuron cell death is reduced in dscaml1 mutant animals, contributing to increased CRH neuron number. Physiologically, dscaml1 mutant animals had significantly higher baseline stress hormone (cortisol) levels and an attenuated response to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that stress axis dysregulation may contribute to the etiology of human DSCAML1-linked neuropsychiatric disorders.

show abstract

Potential involvement of DSCAML1 mutations in neurodevelopmental disorders

Cited by 6 publications

References 47 publications

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Goat SNX29: mRNA expression, InDel and CNV detection, and their associations with litter size

Deficiency in the cell-adhesion moleculedscaml1impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

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