Rods and cones are morphologically and developmentally distinct photoreceptor types with different functions in vision. Cones mediate daylight and color vision and in most mammals express M and S opsin photopigments for sensitivity to medium-long and short light wavelengths, respectively. Rods mediate dim light vision and express rhodopsin photopigment. The transcription factor networks that direct differentiation of each photoreceptor type are incompletely defined. Here, we report that Rorb ؊/؊ mice lacking retinoid-related orphan nuclear receptor ␤ lose rods but overproduce primitive S cones that lack outer segments. The phenotype reflects pronounced plasticity between rod and cone lineages and resembles that described for Nrl ؊/؊ mice lacking neural retina leucine zipper factor. Rorb ؊/؊ mice lack Nrl expression and reexpression of Nrl in Rorb ؊/؊ mice converts cones to rod-like cells. Thus, Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation.cone ͉ differentiation R ods and cones are distinct receptor cell types that mediate dim and bright light vision, respectively. In the mouse, cones are generated between midgestation and birth (1) and subpopulations differentially express M and S opsin photopigments for sensitivity to medium-long and short light wavelengths, respectively (2). Rods express rhodopsin and greatly outnumber cones in mice. Rod generation lags behind that of cones and is more protracted, lasting until about a week after birth. Rods, cones, and other retinal cell types are generated in a stereotypical order from multipotent progenitors, and it has been proposed that a combination of transcription factor activities and external signals at a given developmental stage prompts progenitors to enter specific differentiation pathways (3, 4).The transcription factors that direct the generation of rod and cone precursors and the terminal differentiation of these cell types are incompletely defined. During terminal differentiation of cones, thyroid hormone receptor TR␤2 is required for M opsin induction such that without TR␤2, cones express only S opsin (5). Factors that promote rod differentiation and survival include leucine zipper protein Nrl (6), orphan nuclear receptor Nr2e3 (7, 8), homeodomain proteins Crx and Otx2 (9-11), and retinoblastoma protein Rb (12,13). Nrl induces Nr2e3 expression and these two genes define a transcriptional hierarchy for rod differentiation. Nrl Ϫ/Ϫ mice overproduce S cones at the expense of rods (6) whereas ectopic Nrl expression converts cones to rods (14). Nr2e3 deficiency causes an enhanced cone phenotype and misexpression of cone genes in rods, suggesting that Nr2e3 represses cone genes to maintain the rod phenotype (15-19). Human NRL and NR2E3 mutations result in retinopathy phenotypes (8,20). The above findings suggest that rod and cone precursors share a default differentiation program as cones and that rod differentiation requires the action of additional transcription factors.The Rorb gene encodin...

The strong spin-orbit coupling and the broken inversion symmetry in monolayer transition metal dichalcogenides (TMDs) results in spin-valley coupled band structures. Such a band structure leads to novel applications in the fields of electronics and optoelectronics. Density functional theory calculations as well as optical experiments have focused on spin-valley coupling in the valence band. Here we present magnetotransport experiments on high-quality n-type monolayer molybdenum disulphide (MoS2) samples, displaying highly resolved Shubnikov-de Haas oscillations at magnetic fields as low as 2 T. We find the effective mass 0.7 me, about twice as large as theoretically predicted and almost independent of magnetic field and carrier density. We further detect the occupation of the second spin-orbit split band at an energy of about 15 meV, i.e. about a factor 5 larger than predicted. In addition, we demonstrate an intricate Landau level spectrum arising from a complex interplay between a density-dependent Zeeman splitting and spin and valley-split Landau levels. These observations, enabled by the high electronic quality of our samples, testify to the importance of interaction effects in the conduction band of monolayer MoS2.Monolayer transition metal dichalcogenides (TMDs) such as MoS 2 , MoSe 2 , WS 2 and WSe 2 are twodimensional (2D) semiconductors with band extrema at the corners (K, K -points) of the first Brillouin zone [1]. Due to the strong spin-orbit coupling the spin degeneracy in the K and K valleys is lifted, with opposite spin polarization normal to the layer plane in opposite valleys (see Fig. 2, inset). This peculiar band structure with coupled spin and valley degrees of freedom results in an anomalous Landau level (LL) structure [2][3][4]. Theoretical proposals predict the formation of LLs under the influence of a perpendicular magnetic field that are arranged differently from those in conventional semiconductor quantum wells and graphene [3]. Magnetotransport measurements have recently been performed in monolayer WSe 2 , MoSe 2 and bilayer MoS 2 revealing two-fold degenerate LLs, large effective masses and carrier density dependent Zeeman splitting [5][6][7][8][9]. Previous works on thicker MoS 2 , MoSe 2 and WSe 2 devices have measured the electron LLs structure at the Q and Q conduction band minima, showing the thickness dependence of the band structure in 2D TMDs [10,11]. Here we focus on single layer MoS 2 where for low electron densities electrons clearly reside at the K-K minima of the bandstructure.Here we report transport measurements in high mobility dual-gated monolayer MoS 2 under a perpendicular magnetic field. Our devices show ohmic contacts at temperatures as low as T ≈ 100 mK allowing us to uncover signatures of so far not reported rich interplay of strong spin-orbit coupling and electron-electron interactions. Shubnikov-de Haas (SdH) oscillations appear already at magnetic fields B ≈ 2 T at a temperature of T ≈ 100 mK. From the temperature dependence of the SdH oscillations we measure an...

Monolayer transition metal dichalcogenides (TMDs) hold great promise for future information processing applications utilizing a combination of electron spin and valley pseudospin. This unique spin system has led to observation of the valley Zeeman effect in neutral and charged excitonic resonances under applied magnetic fields. However, reported values of the trion valley Zeeman splitting remain highly inconsistent across studies. Here, we utilize high quality hBN encapsulated monolayer WSe 2 to enable simultaneous measurement of both intervalley and intravalley trion photoluminescence. We find the valley Zeeman splitting of each trion state to be describable only by a combination of three distinct g-factors, one arising from the exciton-like valley Zeeman effect, the other two, trion specific, g-factors associated with recoil of the excess electron. This complex picture goes significantly beyond the valley Zeeman effect reported for neutral excitons, and eliminates the ambiguity surrounding the magneto-optical response of trions in tungsten based TMD monolayers.

SUMMARYDysfunction or death of photoreceptors is the primary cause of vision loss in retinal and macular degenerative diseases. As photoreceptors have an intimate relationship with the retinal pigment epithelium (RPE) for exchange of macromolecules, removal of shed membrane discs and retinoid recycling, an improved understanding of the development of the photoreceptor-RPE complex will allow better design of gene-and cell-based therapies. To explore the epigenetic contribution to retinal development we generated conditional knockout alleles of DNA methyltransferase 1 (Dnmt1) in mice. Conditional Dnmt1 knockdown in early eye development mediated by Rx-Cre did not produce lamination or cell fate defects, except in cones; however, the photoreceptors completely lacked outer segments despite near normal expression of phototransduction and cilia genes. We also identified disruption of RPE morphology and polarization as early as E15.5. Defects in outer segment biogenesis were evident with Dnmt1 exon excision only in RPE, but not when excision was directed exclusively to photoreceptors. We detected a reduction in DNA methylation of LINE1 elements (a measure of global DNA methylation) in developing mutant RPE as compared with neural retina, and of Tuba3a, which exhibited dramatically increased expression in mutant retina. These results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. We also establish a model to study the epigenetic mechanisms and signaling pathways that guide the modulation of photoreceptor outer segment morphogenesis by RPE during retinal development and disease.

Phototransduction machinery in vertebrate photoreceptors is contained within the membrane discs of outer segments. Daily renewal of 10% of photoreceptor outer segments requires stringent control of gene expression. Rhodopsin constitutes over 90% of the protein in rod discs, and its altered expression or transport is associated with photoreceptor dysfunction and/or death. Two cis-regulatory sequences have been identified upstream of the rhodopsin transcription start site. While the proximal promoter binds to specific transcription factors, including NRL and CRX, the rhodopsin enhancer region (RER) reportedly contributes to precise and high-level expression of rhodopsin in vivo. Here, we report the identification of RER-bound proteins by mass spectrometry. We validate the binding of NonO (p54(nrb)), a protein implicated in coupling transcription to splicing, and three NonO-interacting proteins-hnRNP M, Ywhaz and Ppp1ca. NonO and its interactors can activate rhodopsin promoter in HEK293 cells and function synergistically with NRL and CRX. DNA-binding domain of NonO is critical for rhodopsin promoter activation. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analysis demonstrates high occupancy of NonO at rhodopsin and a subset of phototransduction genes. Furthermore, shRNA knockdown of NonO in mouse retina leads to loss of rhodopsin expression and rod cell death, which can be partially rescued by a C-terminal NonO construct. RNA-seq analysis of the NonO shRNA-treated retina revealed splicing defects and altered expression of genes, specifically those associated with phototransduction. Our studies identify an important contribution of NonO and its interacting modulator proteins in enhancing rod-specific gene expression and controlling rod homeostasis.

Atomically thin two-dimensional semiconducting transition metal dichalcogenides (TMDs) can withstand large levels of strain before their irreversible damage occurs. This unique property offers a promising route for control of the optical and electronic properties of TMDs, for instance, by depositing them on nanostructured surfaces, where position-dependent strain can be produced on the nanoscale. Here, we demonstrate strain-induced modifications of the optical properties of mono-and bilayer TMD WSe 2 placed on photonic nanoantennas made from gallium phosphide (GaP). Photoluminescence (PL) from the strained areas of the TMD layer is enhanced owing to the efficient coupling with the confined optical mode of the nanoantenna. Thus, by following the shift of the PL peak, we deduce the changes in the strain in WSe 2 deposited on the nanoantennas of different radii. In agreement with the presented theory, strain up to ≈1.4% is observed for WSe 2 monolayers. We also estimate that >3% strain is achieved in bilayers, accompanied by the emergence of a direct bandgap in this normally indirect-bandgap semiconductor. At cryogenic temperatures, we find evidence of the exciton confinement in the most strained nanoscale parts of the WSe 2 layers, as also predicted by our theoretical model. Our results of direct relevance for both dielectric and plasmonic nanoantennas, show that strain in atomically thin semiconductors can be used as an additional parameter for engineering light−matter interaction in nanophotonic devices.

Strong spin-orbit coupling in transition metal dichalcogenide (TMDC) monolayers results in spin resolvable band structures about the K and K valleys such that the eigenbasis of a 2D quantum dot (QD) in a TMDC monolayer in zero field is described by the Kramers pairs |0 − = |K ↑ , |1 − = |K ↓ and |0 + = |K ↑ , |1 + = |K ↓ . The strong spin-orbit coupling limits the usefulness of single TMDC QDs as spin qubits. Possible regimes of spin-degenerate states, overcoming the spin-orbit coupling in monolayer TMDC QDs are investigated in both zero field, where the spin and valley degrees of freedom become fourfold degenerate, and twofold degeneracy in some magnetic field, localised to a given valley. Such regimes are shown to be achievable in MoS2, where the spin orbit coupling is sufficiently low and of the right sign such that the spin resolved conduction bands intersect at points about the K and K valleys and as such may be exploited by selecting suitable critical dot radii.

Recent experimental studies of out-of-plane straining geometries of transition metal dichalchogenide (TMD) monolayers have demonstrated sufficient band gap renormalisation for device application such as single photon emitters. Here, a simple continuum-mechanical plate-theory approach is used to estimate the topography of TMD monolayers layered atop nanopillar arrays. From such geometries, the induced conduction band potential and band gap renormalisation is given, demonstrating a curvature of the potential that is independent of the height of the deforming nanopillar. Additionally, with a semi-classical WKB approximation, the expected escape rate of electrons in the strain potential may be calculated as a function of the height of the deforming nanopillar. This approach is in accordance with experiment, supporting recent findings suggesting that increasing nanopillar height decreases the linewidth of the single photon emitters observed at the tip of the pillar, and predicting the shift in photon energy with nanopillar height for systems with consistent topography. arXiv:1803.09658v1 [cond-mat.mes-hall]