The role of homeobox gene‐encoded transcription factors in regulation of phototransduction: Implementing the primary pinealocyte culture as a photoreceptor model

Hertz, H; Blancas-Velazquez, Aurea Susana; Rath, Martin F.

doi:10.1111/jpi.12753

Cited by 7 publications

(11 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27 Transcription factors that modulate melatonin synthesis have previously been described as being expressed exclusively in the adult pineal gland and retina, two evolutionary-related tissues that share a substantial overlap of gene expression, specifically homeobox genes. 21,24,50,51 Here, we find the same confined expression pattern for Isl2. Retinal expression of Isl2 is relatively low (100-fold lower than in the pineal gland), likely because it is confined to a subset of retinal ganglion cells in postnatal development.…”

Section: Discussionsupporting

confidence: 76%

“…Transcription factors that modulate melatonin synthesis have previously been described as being expressed exclusively in the adult pineal gland and retina, two evolutionary‐related tissues that share a substantial overlap of gene expression, specifically homeobox genes 21,24,50,51 . Here, we find the same confined expression pattern for Isl2 .…”

Section: Discussionsupporting

confidence: 64%

See 1 more Smart Citation

The ISL LIM‐homeobox 2 transcription factor is negatively regulated by circadian adrenergic signaling to repress the expression of Aanat in pinealocytes of the rat pineal gland

Mattern,

Blancas‐Velázquez,

Ngo

et al. 2023

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Melatonin is synthesized in the pineal gland during nighttime in response to nocturnal increase in the activity of the enzyme aralkylamine N‐acetyltransferase (AANAT), the transcription of which is modulated by several homeodomain transcription factors. Recent work suggests that the homeodomain transcription factor ISL LIM homeobox 2 (ISL2) is expressed in the pineal gland, but its role is currently unknown. With the purpose of identifying the mechanisms that control pineal expression of Isl2 and the possible function of Isl2 in circadian pineal biology, we report that Isl2 is specifically expressed in the pinealocytes of the rat pineal gland. Its expression exhibits a 24 h rhythm with high transcript and protein levels during the day and a trough in the second half of the night. This rhythm persists in darkness, and lesion studies reveal that it requires intact function of the suprachiasmatic nuclei, suggesting intrinsic circadian regulation. In vivo and in vitro experiments show that pineal Isl2 expression is repressed by adrenergic signaling acting via cyclic AMP; further, Isl2 is negatively regulated by the nocturnal transcription factor cone‐rod homeobox. During development, pineal Isl2 expression is detectable from embryonic day 19, preceding Aanat by several days. In vitro knockdown of Isl2 is accompanied by an increase in Aanat transcript levels suggesting that ISL2 represses its daytime expression. Thus, rhythmic expression of ISL2 in pinealocytes is under the control of the suprachiasmatic nucleus acting via adrenergic signaling in the gland to repress nocturnal expression, while ISL2 itself negatively regulates daytime pineal expression of Aanat and thereby suggestively enhances the circadian rhythm in melatonin synthesis.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 64%

The ISL LIM‐homeobox 2 transcription factor is negatively regulated by circadian adrenergic signaling to repress the expression of Aanat in pinealocytes of the rat pineal gland

Mattern,

Blancas‐Velázquez,

Ngo

et al. 2023

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…21,23,39,44 The categories above are defined in the context of the brain, but notably most of the pineal homeobox genes are also to some extent expressed in the retina, 23,45,47,48 supporting the concept that these tissues represent variations on a common theme. 15,17 In the following sections, our focus will be on the role of homeobox genes in development of the pineal gland and regulatory functions in melatonin synthesis of the adult pineal gland, respectively (Table 1).…”

Section: Overview Of Ontogenetic Expression Of Homeobox Genes In the ...mentioning

confidence: 99%

“…46 However, these oscillations are only moderate as compared to 150-fold change in Aanat transcript abundance. 74 Transcripts from most of these homeobox genes are also detectable in the adult rat retina, namely Crx, Otx2, Pax4, Rax, Lhx4, and Isl2, 21,23,45,47,48 but among these, only Pax4 and to a minor extent Lhx4 are rhythmic, 17,21,47 suggesting that rhythmic expression is mainly a feature of pineal homeobox genes.…”

Section: Rhythmic Patterns Of Pineal Homeobox Gene Expressionmentioning

confidence: 99%

Homeobox gene‐encoded transcription factors in development and mature circadian function of the rodent pineal gland

Rath

2024

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene‐encoded transcription factors in developmental and circadian mature neuroendocrine function.

show abstract

“…In lower vertebrates, the pineal gland has direct photosensitivity; however, in mammals, including humans, the pineal gland has lost direct photosensitivity [ 2 , 3 ]. Rodents are often used as experimental animal models and are widely used in the study of regulating pineal melatonin secretion [ 4 , 5 , 6 ]. Melatonin plays a role in a variety of physiological functions in the body, and melatonin deficiency may lead to the impairment of liver and mitochondrial function in nonalcoholic fatty liver disease (NAFLD) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Circ-ERC2 Is Involved in Melatonin Synthesis by Regulating the miR-125a-5p/MAT2A Axis

Guo

Zheng

Zhao

et al. 2022

IJMS

View full text Add to dashboard Cite

The circadian rhythm of melatonin secretion in the pineal gland is highly conserved in vertebrates. Melatonin levels are always elevated at night. Acetylserotonin O-methyltransferase (ASMT) is the last enzyme in the regulation of melatonin biosynthesis (N-acetyl-5-hydroxytryptamine-melatonin). S-adenosylmethionine (SAM) is an important methyl donor in mammals and can be used as a substrate for the synthesis of melatonin. Methionine adenosyltransferase (MAT) catalyzes the synthesis of SAM from methionine and ATP and has a circadian rhythm. CircRNA is an emerging type of endogenous noncoding RNA with a closed loop. Whether circRNAs in the pineal gland can participate in the regulation of melatonin synthesis by binding miRNAs to target mat2a as part of the circadian rhythm is still unclear. In this study, we predicted the targeting relationship of differentially expressed circRNAs, miRNAs and mRNAs based on the results of rat pineal RNA sequencing. Mat2a siRNA transfection confirmed that mat2a is involved in the synthesis of melatonin. Circ-ERC2 and miR-125a-5p were screened out by software prediction, dual-luciferase reporter experiments, cell transfection, etc. Finally, we constructed a rat superior cervical ganglionectomy model (SCGx), and the results showed that circ-ERC2 could participate in the synthesis of melatonin through the miR-125a-5p/MAT2A axis. The results of the study revealed that circ-ERC2 can act as a molecular sponge of miR-125a-5p to regulate the synthesis of melatonin in the pineal gland by targeting mat2a. This experiment provides a basis for research on the circadian rhythm of noncoding RNA on pineal melatonin secretion.

show abstract

The role of homeobox gene‐encoded transcription factors in regulation of phototransduction: Implementing the primary pinealocyte culture as a photoreceptor model

Cited by 7 publications

References 52 publications

The ISL LIM‐homeobox 2 transcription factor is negatively regulated by circadian adrenergic signaling to repress the expression of Aanat in pinealocytes of the rat pineal gland

The ISL LIM‐homeobox 2 transcription factor is negatively regulated by circadian adrenergic signaling to repress the expression of Aanat in pinealocytes of the rat pineal gland

Homeobox gene‐encoded transcription factors in development and mature circadian function of the rodent pineal gland

Circ-ERC2 Is Involved in Melatonin Synthesis by Regulating the miR-125a-5p/MAT2A Axis

Contact Info

Product

Resources

About