Dataset Information

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain.

ABSTRACT: The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc) mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression.We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin) is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b) and cryptochrome 3 (cry3), in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh) and serotonin-N-acetyltransferase (aanat2), involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT) siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their WT siblings.Our data suggests that circadian rhythms can be initiated and maintained in the absence of SCN and other tissues in the ventral brain. However, the SCN may have a role in regulating the amplitude of rhythms when environmental cues are absent. This provides some of the first evidence that the SCN of teleosts is not essential for establishing circadian rhythms during development. Several SCN-independent circadian rhythms have also been found in mammalian species. Thus, zebrafish may serve as a model system for understanding how vertebrate embryos coordinate rhythms that are controlled by different circadian clocks.

SUBMITTER: Noche RR

PROVIDER: S-EPMC3031267 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain.

Noche Ramil R RR Lu Po-Nien PN Goldstein-Kral Lauren L Glasgow Eric E Liang Jennifer O JO

BMC neuroscience 20110113

<h4>Background</h4>The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc) mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the ...[more]

PMID: 21232144

Similar Datasets

Project description:Circadian rhythm disorder is a common, but often neglected, consequence of neonatal hypoxic-ischemic brain damage (HIBD). However, the underlying molecular mechanisms remain largely unknown. We previously showed that, in a rat model of HIBD, up-regulation of microRNA-325 (miR-325) in the pineal gland is responsible for the suppression of Aanat, a key enzyme involved in melatonin synthesis and circadian rhythm regulation. To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD, we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University (Dushuhu Branch) in 2019. We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD. Furthermore, a luciferase reporter gene assay revealed that LIM homeobox 3 (LHX3) is a novel downstream target of miR-325. In addition, in miR-325 knock-down mice, the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland. We established a neonatal mouse model of HIBD by performing double-layer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours. Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions. Finally, we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3. Taken together, our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD. The clinical trial was approved by Institutional Review Board of Children's Hospital of Soochow University (approval No. 2015028) on July 20, 2015. Animal experiments were approved by Animal Care and Use Committee, School of Medicine, Soochow University, China (approval No. XD-2016-1) on January 15, 2016.

Project description:Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in various life processes, including circadian rhythms. Although next generation sequencing technologies have facilitated faster profiling of lncRNAs, the resulting datasets require sophisticated computational analyses. In particular, the regulatory roles of lncRNAs in circadian clocks are far from being completely understood. In this study, we conducted RNA-seq-based transcriptome analysis of zebrafish larvae under both constant darkness (DD) and constant light (LL) conditions in a circadian manner, employing state-of-the-art computational approaches to identify approximately 3220 lncRNAs from zebrafish larvae, and then uncovered 269 and 309 lncRNAs displaying circadian rhythmicity under DD and LL conditions, respectively, with 30 of them are coexpressed under both DD and LL conditions. Subsequently, GO, COG, and KEGG pathway enrichment analyses of all these circadianly expressed lncRNAs suggested their potential involvement in numerous biological processes. Comparison of these circadianly expressed zebrafish larval lncRNAs, with rhythmically expressed lncRNAs in the zebrafish pineal gland and zebrafish testis, revealed that nine (DD) and twelve (LL) larval lncRNAs are coexpressed in the zebrafish pineal gland and testis, respectively. Intriguingly, among peptides encoded by these coexpressing circadianly expressed lncRNAs, three peptides (DD) and one peptide (LL) were found to have the known domains from the Protein Data Bank. Further, the conservation analysis of these circadianly expressed zebrafish larval lncRNAs with human and mouse genomes uncovered one lncRNA and four lncRNAs shared by all three species under DD and LL conditions, respectively. We also investigated the conserved lncRNA-encoded peptides and found one peptide under DD condition conserved in these three species and computationally predicted its 3D structure and functions. Our study reveals that hundreds of lncRNAs from zebrafish larvae exhibit circadian rhythmicity and should help set the stage for their further functional studies.

Dataset Information

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain.

Publications

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets