MiRNA expression in the eye

Huang, Kristen M.; Dentchev, Tzvete; Stambolian, Dwight

doi:10.1007/s00335-008-9127-8

Cited by 32 publications

(23 citation statements)

References 33 publications

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“…MicroRNAs with retinal-restricted expression have been reported (Alfano et al, 2005; Conte et al, 2010a;Huang et al, 2008), pointing to this mechanism as an attractive possibility. Graded expression might be also a direct consequence of Sox2 regulation.…”

Section: Research Articlementioning

confidence: 99%

Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning

et al. 2012

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SUMMARYThe vertebrate forebrain is patterned during gastrulation into telencephalic, retinal, hypothalamic and diencephalic primordia. Specification of each of these domains requires the concerted activity of combinations of transcription factors (TFs). Paradoxically, some of these factors are widely expressed in the forebrain, which raises the question of how they can mediate regional differences. To address this issue, we focused on the homeobox TF Six3.2. With genomic and functional approaches we demonstrate that, in medaka fish, Six3.2 regulates, in a concentration-dependent manner, telencephalic and retinal specification under the direct control of Sox2. Six3.2 and Sox2 have antagonistic functions in hypothalamic development. These activities are, in part, executed by Foxg1 and Rx3, which seem to be differentially and directly regulated by Six3.2 and Sox2. Together, these data delineate the mechanisms by which Six3.2 diversifies its activity in the forebrain and highlight a novel function for Sox2 as one of the main regulators of anterior forebrain development. They also demonstrate that graded levels of the same TF, probably operating in partially independent transcriptional networks, pattern the vertebrate forebrain along the anterior-posterior axis. Exploiting these advantages, here we delineate a gene regulatory network in which Six3.2 diversifies its activity in the forebrain. We demonstrate that differential expression levels of Six3.2, operating under the differential control of Sox2, are likely to pattern the forebrain by directly activating the telencephalic determinant Foxg1 (Tao and Lai, 1992), restraining, at the same time, the expression of the hypothalamic and retinal determinant Rx3 (Deschet et al., 1999;Loosli et al., 2001;Stigloher et al., 2006). We also show that Sox2, besides controlling Six3.2 expression, activates that of Rx3, thus establishing a four gene 'kernel' that contributes to forebrain specification. MATERIALS AND METHODS Medaka stocksWild-type (wt) Oryzias latipes of the cab strain were maintained in an inhouse facility (28°C on a 14/10-hour light/dark cycle). Embryos were staged according to Iwamatsu (Iwamatsu, 2004). In silico analysisJaspar (http://jaspar.genereg.net) and rVista (http://rvista.dcode.org/) were used to identify putative TF binding sites (BSs) within the Six3.2 regulatory region, setting the core identity to ≥90%. Positive sites were further screened for evolutionary conservation by phylogenetic footprinting among different teleost species (Fugu rubripes, Gasteropus aculeatus, Tetraodon nigroviridis and Danio rerio) using mVista (http://genome.lbl.gov/vista/ mvista/about.shtml) and multalin (http://multalin.toulouse.inra.fr/multalin). Identified candidates were further selected using expression pattern information available in the literature and in the ZFIN database (http://zfin.org). Plasmid constructionThe thymidine kinase (TK) minimal promoter was cloned into the pGL3-basic vector (Promega) to generate pGL3bTK, into which was then inserted PCR-amplified co...

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Section: Research Articlementioning

confidence: 99%

Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning

et al. 2012

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“…This review will focus on two main classes-miRNAs and long, mRNA-like ncRNAs of unknown mechanism of action-and discuss what is known about the mechanism of action and cellular targets of these molecules. Several recent reviews have covered related topics, and it is recommended that the reader refer to these for additional perspective on the topic of retinal ncRNAs Huang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

New meaning in the message: Noncoding RNAs and their role in retinal development

Rapicavoli

Blackshaw

2009

Developmental Dynamics

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Recent studies have indicated that non-protein-coding RNAs (ncRNAs) may play prominent and diverse roles in the development of the nervous system. These ncRNAs are now known to perform a broad range of cellular functions, and in particular appear to be prominent players in the regulation of transcription and translation. In this review, we discuss recent advances in our understanding of the role of ncRNAs in vertebrate retinal development. Noncoding RNAs that are known or suspected to play a functional role in the specification and maturation of retinal cell subtypes include miRNAs, long noncoding opposite-strand transcripts (OSTs), and other long ncRNAs such as Tug1 and RNCR2. Though the mechanism of action of most of these ncRNAs is still largely unclear, it is likely that these molecules represent a major, and thus far largely unappreciated, component of the molecular machinery involved in retinal cell fate specification.

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“…Our last elimination criterion was that the candidate miRNA must be highly expressed in the retina. Recently, several miRNAs have been shown to be highly or specifically expressed in the eye (7,(37)(38)(39). MicroRNA-96 is exclusively expressed in the retina photoreceptor layer.…”

Section: L-vgcc␣1c Is a Downstream Target Of Mir-26a-to Inves-mentioning

confidence: 99%

Rhythmic Expression of MicroRNA-26a Regulates the L-type Voltage-gated Calcium Channel α1C Subunit in Chicken Cone Photoreceptors

Shi

2009

Journal of Biological Chemistry

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MicroRNAs (miRNAs) modulate gene expression by degrading or inhibiting translation of messenger RNAs (mRNAs).Here, we demonstrated that chicken microRNA-26a (gga-mir-26a) is a key posttranscriptional regulator of photoreceptor L-type voltage-gated calcium channel ␣1C subunit (L-VGCC␣1C) expression, and its own expression has a diurnal rhythm, thereby explaining the rhythmic nature of L-VGCC␣1Cs. Circadian oscillators in retinal photoreceptors provide a mechanism that allows photoreceptors to anticipate daily illumination changes. In photoreceptors, L-VGCC activities are under circadian control, which are higher at night and lower during the day. Interestingly, the mRNA level of VGCC␣1D oscillates, but those for VGCC␣1C do not. However, the protein expression of both VGCC␣1C and ␣1D are higher at night in cone photoreceptors. The underlying mechanism regulating L-VGCC␣1C protein expression was not clear until now. In vitro targeting reporter assays verified that gga-mir-26a specifically targeted the L-VGCC␣1C 3-untranslated region, and gga-mir-26a expression in the retina peaked during the day. After transfection with gga-mir-26a, L-VGCC␣1C protein expression and L-VGCC current density decreased. Therefore, the rhythmic expression of gga-mir-26a regulated the protein expression of the L-VGCC␣1C subunit. Additionally, both CLOCK (circadian locomoter output cycles kaput) and CREB (cAMP-response element-binding protein-1) activated gga-mir-26a expression in vitro. This result implies that gga-mir-26a might be a downstream target of circadian oscillators. Our work has uncovered new functional roles for miRNAs in the regulation of circadian rhythms in cone photoreceptors. Circadian regulated miRNAs could serve as the link between the core oscillator and output signaling that further govern biological functions. MicroRNAs (miRNAs)2 are a group of short, non-coding, single-stranded RNAs ϳ23 nucleotides in size, and they are regulatory elements targeting one or more downstream messenger RNAs (mRNAs), causing posttranscriptional degradation or translational repression (1-3). The mature miRNA is derived from a precursor sequence, which is transcribed from the genome by either RNA polymerase II or III, and miRNA expression shows tissue and developmental stage-specific patterns (1). Recently, several miRNAs have been reported to be involved in circadian rhythm (2-5). MicroRNA-219 and mir-132 influence the core oscillator in the mouse suprachiasmatic nucleus (SCN), the master clock. In vivo knockdown of mir-219 lengthens the circadian period, and mir-132 modulates lightinduced clock resetting in mice (6). In the mouse retina, several miRNAs with high expression levels have been reported to be under circadian control. MicroRNA-182, mir-183, and mir-96 form a cluster in mouse chromosome 7, and they are highly expressed in the photoreceptor layer (7). Other miRNAs, such as mir-181a, mir-125b, mir-26a, mir-124a, mir-204, and mir30c are expressed in different retina neurons, including photoreceptors (5,7,8). Whereas the mir-182/18...

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MiRNA expression in the eye

Cited by 32 publications

References 33 publications

Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning

Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning

New meaning in the message: Noncoding RNAs and their role in retinal development

Rhythmic Expression of MicroRNA-26a Regulates the L-type Voltage-gated Calcium Channel α1C Subunit in Chicken Cone Photoreceptors

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