Multiple Functions of the Dmrt Genes in the Development of the Central Nervous System

Kikkawa, Takako; Osumi, Noriko

doi:10.3389/fnins.2021.789583

Cited by 10 publications

(10 citation statements)

References 117 publications

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“…As shown in Figure 3 , Dmrt1 , Dmrt2a , Dmrt3 , and Dmrt5 were found in all five teleost species. As expected, Dmrt genes were clustered into six subfamilies, which is consistent with previous studies ( Dong et al, 2020 ; Kikkawa and Osumi, 2021 ), and each Dmrt gene branched along with its counterparts from different vertebrate species. Within each subfamily, the phylogenetic topology could be further divided into two subgroups: tetrapods and teleosts.…”

Section: Resultssupporting

confidence: 92%

Genome-Wide Identification, Phylogeny, and Expression Profile of the Dmrt (Doublesex and Mab-3 Related Transcription Factor) Gene Family in Channel Catfish (Ictalurus punctatus)

Zhang

et al. 2022

Front. Genet.

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The Dmrt (Doublesex and Mab-3 related transcription factor) gene family is a class of crucial transcription factors characterized by a conserved DM domain related to sex determination and differentiation, which has been systematically described in various teleost fish, but less in channel catfish (Ictalurus punctatus), an important global aquaculture species in the US and China. In this study, seven Dmrt genes from channel catfish genome were identified and analyzed using bioinformatics methods. Seven IpDmrt genes were distributed unevenly across five chromosomes. Synteny analysis revealed that Dmrt1, Dmrt2a, Dmrt2b, Dmrt3, Dmrt4, and Dmrt5 were relatively conserved in teleost fish. Tissue distribution analysis showed that IpDmrt1, IpDmrt2b, IpDmrt5, and IpDmrt6 exhibited sexually dimorphic expression patterns and, among them, IpDmrt1 and IpDmrt6 had high expression levels in the testes, while IpDmrt2b and IpDmrt5 had more significant expression levels in the ovaries than in other tissues. After 17β-estradiol treatment, IpDmrt2b and IpDmrt5 were significantly up regulated, while the expression of IpDmrt1 and IpDmrt6 was significantly repressed in XY channel catfish ovaries compared with XX channel catfish ovaries. The present study provides a comprehensive insight into the Dmrt gene family of channel catfish. The results suggest that IpDmrt1 and IpDmrt6 may play an important role in testis differentiation/development, while IpDmrt2b and IpDmrt5 are critical in ovary development in this species.

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Section: Resultssupporting

confidence: 92%

Genome-Wide Identification, Phylogeny, and Expression Profile of the Dmrt (Doublesex and Mab-3 Related Transcription Factor) Gene Family in Channel Catfish (Ictalurus punctatus)

Zhang

et al. 2022

Front. Genet.

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“…Evidence of DMRT2 was limited in the early linkage studies and 9p deletion-related studies. As was observed, catastrophic deletion of DMRTs may lead to severe functional disorders like intellectual disability in 9p deletion patients, or lead to abnormality in the macro-structure of the brain in knock-out mice (19,20). SNPs with minor effects may also affect the brain at a smaller scale prenatally.…”

Section: Discussionmentioning

confidence: 84%

“…They play a conserved role in sexual development and other developmental processes like neural development (18). According to current literature, DMRTs were essential genes for the central nervous system during early embryonic development, playing critical roles in brain patterning, corticogenesis, and other neurogenesis processes (19,20). Previous studies suggested a putative gene in distal 9p associated with OCD (21,22).…”

Section: Introductionmentioning

confidence: 99%

Exploring Association Between Serotonin and Neurogenesis Related Genes in Obsessive-Compulsive Disorder in Chinese Han People: Promising Association Between DMRT2, miR-30a-5p, and Early-Onset Patients

Deng

Wang

et al. 2022

Front. Psychiatry

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Obsessive-compulsive disorder (OCD) is a deliberating disorder with complex genetic and environmental etiologies. Hypotheses about OCD mainly include dysregulated neurotransmitters, especially serotonin, and disturbed neurodevelopment. Single nucleotide polymorphism (SNP) association studies regarding OCD are often met with inconsistent results. However, stratification by age of onset may sometimes help to limit the heterogenicity of OCD patients. Therefore, we conducted a stratified SNP association study enrolling 636 patients and 612 healthy controls. Patients were stratified by age of onset as early-onset (EO-OCD) and late-onset (LO-OCD). Blood extracted from the patients was used to genotype 18 loci, including serotonin system genes, Slitrk1, Slitrk5, and DMRT2 and related miRNA genes. Logistic regression was used to compare allele and genotype frequencies of variants. A general linear model was used to evaluate the association between variants and trait anxiety. In our study, rs3824419 in DMRT2 was associated with EO-OCD, G allele was the risk allele. Rs2222722 in miR-30a-5p was associated with EO-OCD, with the C allele being the risk allele. Rs1000952 in HTR3D was found associated with trait anxiety in OCD patients. The significance disappeared after FDR correction. Our results supported neurodevelopment-related genes, DMRT2 and miR-30a-5p, to be related to EO-OCD. However, we cannot prove serotonin genes to be directly associated with EO-OCD. While an association between HTR3D and trait anxiety was discovered, comparisons based on biological or clinical traits may be helpful in future studies. As our detective powers were limited, more large-scale studies will be needed to confirm our conclusion.

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“…These novel pathways, i.e., Pax6 → Dmrta1 → Ngn2-|Ascl1 and/or Pax6 → Dmrta1-|Ascl1, could determine progenitor cell DV identity by repressing ventralization. For more information on the roles of Dmrt family members in brain patterning, see the review in [ 78 ]. As described in this section, Pax6 promotes brain development via numerous downstream factors to maintain proper AP and DV patterning in the telencephalon.…”

Section: Pax6 In Cortical Patterningmentioning

confidence: 99%

Thirty Years’ History since the Discovery of Pax6: From Central Nervous System Development to Neurodevelopmental Disorders

Ochi

Manabe

Kikkawa

et al. 2022

IJMS

Self Cite

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Pax6 is a sequence-specific DNA binding transcription factor that positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system (CNS). As indicated by the morphological and functional abnormalities in spontaneous Pax6 mutant rodents, Pax6 plays pivotal roles in various biological processes in the CNS. At the initial stage of CNS development, Pax6 is responsible for brain patterning along the anteroposterior and dorsoventral axes of the telencephalon. Regarding the anteroposterior axis, Pax6 is expressed inversely to Emx2 and Coup-TF1, and Pax6 mutant mice exhibit a rostral shift, resulting in an alteration of the size of certain cortical areas. Pax6 and its downstream genes play important roles in balancing the proliferation and differentiation of neural stem cells. The Pax6 gene was originally identified in mice and humans 30 years ago via genetic analyses of the eye phenotypes. The human PAX6 gene was discovered in patients who suffer from WAGR syndrome (i.e., Wilms tumor, aniridia, genital ridge defects, mental retardation). Mutations of the human PAX6 gene have also been reported to be associated with autism spectrum disorder (ASD) and intellectual disability. Rodents that lack the Pax6 gene exhibit diverse neural phenotypes, which might lead to a better understanding of human pathology and neurodevelopmental disorders. This review describes the expression and function of Pax6 during brain development, and their implications for neuropathology.

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Multiple Functions of the Dmrt Genes in the Development of the Central Nervous System

Cited by 10 publications

References 117 publications

Genome-Wide Identification, Phylogeny, and Expression Profile of the Dmrt (Doublesex and Mab-3 Related Transcription Factor) Gene Family in Channel Catfish (Ictalurus punctatus)

Genome-Wide Identification, Phylogeny, and Expression Profile of the Dmrt (Doublesex and Mab-3 Related Transcription Factor) Gene Family in Channel Catfish (Ictalurus punctatus)

Exploring Association Between Serotonin and Neurogenesis Related Genes in Obsessive-Compulsive Disorder in Chinese Han People: Promising Association Between DMRT2, miR-30a-5p, and Early-Onset Patients

Thirty Years’ History since the Discovery of Pax6: From Central Nervous System Development to Neurodevelopmental Disorders

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