Molecular Evolution and Subfunctionalization of Nkx2.1 in the Rainbow Trout

Suzuki, Masakazu; Hidaka, Yoshio; Uemae, Youji; Tanaka, Shigeyasu

doi:10.1196/annals.1327.096

Cited by 4 publications

(5 citation statements)

References 4 publications

(8 reference statements)

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“…In addition, Pax9 is expressed in mammalian thyroid cell lines, although it does not mediate transcription from a 2-kb calcitonin (CT) promoter (Suzuki et al 2007) (see Table 1 for a list of endocrine organs and their secretions). In teleost fish, Pax1 and Pax9 are also expressed in the untimobranchial gland, a pharyngeal derivative (Suzuki et al 2005(Suzuki et al , 2007. Pax2 is also expressed in pancreatic islets, where it transcriptionally activates glucagon (Ritz-Laser et al 2000).…”

Section: The Evolution Of Chordate Pax Genesmentioning

confidence: 99%

Alternative Splicing in Development and Function of Chordate Endocrine Systems: A Focus on Pax Genes

Holland

Short²

2010

Integrative and Comparative Biology

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Genome sequencing has facilitated an understanding of gene networks but has also shown that they are only a small part of the answer to the question of how genes translate into a functional organism. Much of the answer lies in epigenetics-heritable traits not directly encoded by the genome. One such phenomenon is alternative splicing, which affects over 75% of protein coding genes and greatly amplifies the number of proteins. Although it was postulated that alternative splicing and gene duplication are inversely proportional and, therefore, have similar effects on the size of the proteome, for ancient duplications such as occurred in the Pax family of transcription factors, that is not necessarily so. The importance of alternative splicing in development and physiology is only just coming to light. However, several techniques for studying isoform functions both in vitro and in vivo have been recently developed. As examples of what is known and what is yet to be discovered, this review focuses on the evolution and roles of the Pax family of transcription factors in development and on alternative splicing of endocrine genes and the factors that regulate them.

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Section: The Evolution Of Chordate Pax Genesmentioning

confidence: 99%

Alternative Splicing in Development and Function of Chordate Endocrine Systems: A Focus on Pax Genes

Holland

Short²

2010

Integrative and Comparative Biology

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“…In zebrafish larvae, BPAF exposure decreases T3 and T4 levels and affects the expression of hypothalamus‐pituitary axis‐related genes, thereby causing thyroid endocrine disorders 41 . In this study, the expression levels of TH receptors ( trhr2 , trhra , trhrb , and thra ) and a gene related to the differentiation of thyroid follicular cells ( nkx2.1 ) have been evaluated 37,42–46 . Exposure to high concentrations of BPAF (5 mg/L) significantly damaged the thyroid function of embryos.…”

Section: Discussionmentioning

confidence: 99%

“…41 In this study, the expression levels of TH receptors (trhr2, trhra, trhrb, and thra) and a gene related to the differentiation of thyroid follicular cells (nkx2.1) have been evaluated. 37,[42][43][44][45][46] Exposure to high concentrations of BPAF (5 mg/L) significantly damaged the thyroid function of embryos.…”

Section: Bpaf Exposure Affects Thyroid Function In Marine Medaka Embryosmentioning

confidence: 99%

Toxic effects of bisphenol AF on the embryonic development of marine medaka (Oryzias melastigma)

Huang

Gao

Chen

et al. 2023

Environmental Toxicology

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Bisphenol AF (BPAF), an emerging environmental endocrine disruptor, has been detected in surface waters worldwide and has adverse effects on aquatic organisms. The accumulation of BPAF in oceans and its potential toxic effect on marine organisms are important concerns. In this study, the effects of BPAF (10, 100, 1, and 5 mg/L) on marine medaka (Oryzias melastigma) were evaluated, including effects on the survival rate, heart rate, hatchability, morphology, and gene expression in embryos. The survival rate of marine medaka embryos was significantly lower after treatment with 5 mg/L BPAF than in the solvent control group. Exposure to 1 mg/L and 5 mg/L BPAF significantly reduced hatchability. Low‐dose BPAF (10 μg/L) significantly accelerated the heart rate of embryos, while high‐dose BPAF (5 mg/L) significantly decreased the heart rate. BPAF exposure also resulted in notochord curvature, pericardial edema, yolk sac cysts, cardiovascular bleeding, and caudal curvature in marine medaka. At the molecular level, BPAF exposure affected the transcript levels of genes involved in the thyroid system (dio1, dio3a, trhr2, tg, and thra), cardiovascular system (gata4, atp2a1, and cacna1da), nervous system (elavl3 and gap43), and antioxidant and inflammatory systems (sod, pparβ, and il‐8) in embryos. These results indicate that BPAF exposure can alter the expression of functional genes, induce abnormal development, and reduce the hatching and survival rates in marine medaka embryos. Overall, BPAF can adversely affect the survival and development of marine medaka embryos, and BPAF may not be an ideal substitute for BPA.

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“…Yet, infusion of Mc4r antagonists mitigates the decreased feeding caused by TTF-1 antisense oligonucleotide (Kim et al, 2011). Mc4r acts as a functional receptor for POMC (Zhang et al, 2012) stimulated promoter transcription, comparable to Nkx2.1b, while Nkx2.1c only induced weak transcription and had different functions (Suzuki et al, 2005). In mandarin fish, Nkx2.1 contains three transcripts, and the most conserved transcript was selected to construct an overexpression vector.…”

Section: Discussionmentioning

confidence: 99%

“…The difference between the results of this experiment and those of mammals might be attributed to the fact that NKX2.1 has multiple copies in various species, and there are certain differences in functions between copies. In fish, Nkx2.1 in rainbow trout has four copies due to genome‐wide replication, among which Nkx2.1a and Nkx2.1c were found to be unique differentiation types of teleost fish, and each copy had different effects on the transcriptional activity of the promoter, and the luciferase intensity showed that Nkx2.1a significantly stimulated promoter transcription, comparable to Nkx2.1b, while Nkx2.1c only induced weak transcription and had different functions (Suzuki et al, 2005). In mandarin fish, Nkx2.1 contains three transcripts, and the most conserved transcript was selected to construct an overexpression vector.…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of NK homeobox 1 (NKX2.1) on melanocortin 4 receptor (Mc4r) promoter in Mandarin fish

Xu,

He,

Liang

et al. 2023

Journal Cellular Physiology

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The melanocortin 4 receptor (MC4R) is a G protein‐coupled transporter that mediates the regulation of thyroid hormones and leptin on energy balance and food intake. However, the mechanisms of transcriptional regulation of Mc4r by thyroid hormone and leptin in fish have been rarely reported. The messenger RNA expression of Mc4r gene was significantly higher in brain than those in other tissues of mandarin fish. We analyzed the structure and function of a 2029 bp sequence of Mc4r promoter. Meanwhile, overexpression of NKX2.1 and incubation with leptin significantly increased Mc4r promoter activity, but triiodothyronine showed the opposite effect. In addition, mutations in the NKX2.1 binding site abolished not only the activation of Mc4r promoter activity by leptin but also the inhibitory effect of thyroid hormones on Mc4r promoter activity. In summary, these results suggested that thyroid hormones and leptin might regulate the transcriptional expression of Mc4r through NKX2.1.

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Molecular Evolution and Subfunctionalization of Nkx2.1 in the Rainbow Trout

Cited by 4 publications

References 4 publications

Alternative Splicing in Development and Function of Chordate Endocrine Systems: A Focus on Pax Genes

Alternative Splicing in Development and Function of Chordate Endocrine Systems: A Focus on Pax Genes

Toxic effects of bisphenol AF on the embryonic development of marine medaka (Oryzias melastigma)

Regulatory effect of NK homeobox 1 (NKX2.1) on melanocortin 4 receptor (Mc4r) promoter in Mandarin fish

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