ORCID Profile
0000-0002-3293-6327
Current Organisations
University of Western Australia
,
Lions Eye Institute
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-05-2019
Abstract: Vertebrates are typically thought to have a consistent system for processing light, in which multiple cone opsins permit color vision during the day, but a single rod opsin provides only monochrome vision in the dark. Musilova et al. analyzed more than 100 deep-sea fish genomes and found a previously unknown proliferation of rod opsin genes that generate rod opsin photopigments that are tuned to different wavelengths of light. These receptors may allow the fish to perceive bioluminescent signals that pervade their deep-sea environment. These results reveal a previously undescribed visual system that allows for color vision in the dark. Science , this issue p. 588
Publisher: Informa UK Limited
Date: 04-03-2016
DOI: 10.3109/09537104.2016.1145202
Abstract: The physiological functions and cellular signaling of Class II phosphoinositide 3-kinases (PI3Ks) remain largely unknown. Platelets express two Class II PI3Ks: PI3KC2α and PI3KC2β. PI3KC2α deficiency was recently reported to cause disruption of the internal membrane reserve structure of platelets (open canalicular system, OCS) that results in dysregulated platelet adhesion and impaired arterial thrombosis in vivo. Notably, these effects on platelets occurred despite normal agonist-induced 3-phosphorylated phosphoinositide (3-PPI) production and cellular activation in PI3KC2α-deficient platelets. However, the potential compensatory actions of PI3KC2β in platelets have not yet been investigated. Here, we report the first mice deficient in both PI3KC2α and PI3KC2β (no Class II PI3Ks in platelets) and reveal a nonredundant role for PI3KC2α in mouse platelet structure and function. Specifically, we show that the disrupted OCS and impaired thrombus stability observed in PI3KC2α-deficient platelets does not occur in PI3KC2β-deficient platelets and is not exaggerated in platelets taken from mice deficient in both enzymes. Furthermore, detailed examination of 3-PPI production in platelets from this series of mice revealed no changes in either unactivated or activated platelets, including those with a complete lack of Class II PI3Ks. These findings indicate a nonredundant role for PI3KC2α in regulating platelet structure and function, and suggest that Class II PI3Ks do not significantly contribute to the acute agonist-induced production of 3-PPIs in these cells.
Publisher: Wiley
Date: 09-07-2012
Publisher: Frontiers Media SA
Date: 11-07-2022
DOI: 10.3389/FNANA.2022.945344
Abstract: Salmonids are ideal models as many species follow a distinct developmental program from demersal eggs and a large yolk sac to hatching at an advanced developmental stage. Further, these economically important teleosts inhabit both marine- and freshwaters and experience erse light environments during their life histories. At a genome level, salmonids have undergone a salmonid-specific fourth whole genome duplication event (Ss4R) compared to other teleosts that are already more genetically erse compared to many non-teleost vertebrates. Thus, salmonids display phenotypically plastic visual systems that appear to be closely related to their anadromous migration patterns. This is most likely due to a complex interplay between their larger, more gene-rich genomes and broad spectrally enriched habitats however, the molecular basis and functional consequences for such ersity is not fully understood. This study used advances in genome sequencing to identify the repertoire and genome organization of visual opsin genes (those primarily expressed in retinal photoreceptors) from six different salmonids [Atlantic salmon ( Salmo salar ), brown trout ( Salmo trutta ), Chinook salmon ( Oncorhynchus tshawytcha ), coho salmon ( Oncorhynchus kisutch ), rainbow trout ( Oncorhynchus mykiss ), and sockeye salmon ( Oncorhynchus nerka )] compared to the northern pike ( Esox lucius ), a closely related non-salmonid species. Results identified multiple orthologues for all five visual opsin classes, except for presence of a single short-wavelength-sensitive-2 opsin gene. Several visual opsin genes were not retained after the Ss4R duplication event, which is consistent with the concept of salmonid rediploidization. Developmentally, transcriptomic analyzes of Atlantic salmon revealed differential expression within each opsin class, with two of the long-wavelength-sensitive opsins not being expressed before first feeding. Also, early opsin expression in the retina was located centrally, expanding dorsally and ventrally as eye development progressed, with rod opsin being the dominant visual opsin post-hatching. Modeling by spectral tuning analysis and atomistic molecular simulation, predicted the greatest variation in the spectral peak of absorbance to be within the Rh2 class, with a ∼40 nm difference in λ max values between the four medium-wavelength-sensitive photopigments. Overall, it appears that opsin duplication and expression, and their respective spectral tuning profiles, evolved to maximize specialist color vision throughout an anadromous lifecycle, with some visual opsin genes being lost to tailor marine-based vision.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2015
DOI: 10.1038/NCOMMS7535
Abstract: PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2α in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations in the platelet internal membrane lead to enhanced membrane tether formation that is associated with accelerated, yet highly unstable, thrombus formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2α-deficient platelets. These findings demonstrate an important role for PI3KC2α in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling. These studies provide a link between the open canalicular system and platelet adhesive function that has relevance to the primary haemostatic and prothrombotic function of platelets.
Publisher: Cold Spring Harbor Laboratory
Date: 23-09-2018
DOI: 10.1101/424895
Abstract: Vertebrate vision is accomplished through a set of light-sensitive photopigments, which are located in the photoreceptors of the retina and consist of a visual opsin protein bound to a chromophore. In dim-light, vertebrates generally rely upon a single rod opsin (RH1) for obtaining visual information. By inspecting 101 fish genomes, we found that three deep-sea teleost lineages have independently expanded their RH1 gene repertoires. Amongst these, the silver spinyfin ( Diretmus argenteus Johnson 1863) stands out as having the highest number of visual opsins known for animals to date (2 cone and 38 rod opsins). Spinyfins simultaneously express up to 14 RH1s encoding for photopigments with different peak spectral sensitivities (λ max =448-513 nm) that cover the range of the residual daylight, as well as the bioluminescence spectrum present in the deep-sea. Our findings present novel molecular and functional evidence for the recurrent evolution of multiple rod opsin-based vision in vertebrates. Contrary to the single rod opsin used by most vertebrates, some fishes use multiple rod opsins for vision in the dimly lit deep-sea.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-11-2017
Abstract: Deep-sea fishes evolved an unconventional visual system to optimize vision in twilight conditions.
Publisher: Frontiers Media SA
Date: 26-04-2017
Publisher: Cold Spring Harbor Laboratory
Date: 27-03-2022
DOI: 10.1101/2022.03.25.485754
Abstract: The complex visually mediated behaviors of diurnal lizards are enabled by a retina typically containing five types of opsins with the potential for tetrachromatic color vision. Despite lizards using a wide range of color signals, the limited variation in photoreceptor spectral sensitivities across lizards suggests only weak selection for species-specific, spectral tuning of photoreceptors. Some species, however, have enhanced short wavelength sensitivity, which likely helps with the detection of signals rich in ultraviolet and short wavelengths. In this study, we examined the visual system of Tiliqua rugosa , which has a UV/blue tongue, to determine the spectral sensitivity of the eye and to gain insight into this species’ visual ecology. Electroretinograms coupled with spectral stimulation showed peak sensitivity at 560 nm with high similarity to other lizards at wavelengths greater than 530 nm. However, at shorter wavelengths, sensitivity is enhanced leading to a spectral sensitivity curve that is 28 nm broader (full width at half height) than other lizards studied so far. The width of the curve is partially explained by a population of photoreceptors that respond more strongly to low temporal frequencies with possible peaks in sensitivity between 460 and 470 nm suggesting that they are SWS2 photoreceptors. The lack of a peak in sensitivity at 360 nm at low temporal frequencies and under a monochromatic light that suppresses the response of LWS photoreceptors, suggests that the SWS1 photoreceptors are red-shifted. In addition, the yellow and green oil droplets that are common in other diurnal lizards appear to be missing and instead, only transparent and pale-yellow oil droplets are present. LWS photoreceptors are likely paired with pale-yellow oil droplets to produce LWS photoreceptors with wider spectral sensitivity curves than in other lizards. Opsin sequencing reveals SWS1, SWS2, RH1, RH2 and LWS opsin genes that are very similar to the visual opsins detected in the green anole, Anolis carolinensis , suggesting there is little change in the spectral sensitivity of photoreceptors compared to other diurnal lizards. Since we only obtained a partial sequence of the SWS1 opsin, we were unable to determine whether amino acid substitution at tuning sites could have played a role in red-shifting the SWS1 photoreceptor spectral sensitivity. Photoreceptor densities are typically higher in central and ventral retinal regions than in the dorsal retina suggesting that higher spatial s ling is necessary at eye level and above the animal than on the ground. However, the SWS1 photoreceptors do not follow this pattern potentially due to their low abundance making them less relevant to high acuity visual tasks. Our findings demonstrate that there are possibly multiple mechanisms acting synergistically in the visual system of T. rugosa to enhance short wavelength sensitivity between 360 and 530 nm. While it is tempting to suggest that this is an adaptation to facilitate the detection of the blue tongues of conspecifics, additional experiments are necessary to determine its ecological relevance. Color vision and the distribution of photoreceptor subtypes in T. rugosa
Publisher: Elsevier BV
Date: 08-2009
Publisher: The Company of Biologists
Date: 06-2022
DOI: 10.1242/JEB.244317
Abstract: Despite lizards using a wide range of colour signals, the limited variation in photoreceptor spectral sensitivities across lizards suggests only weak selection for species-specific, spectral tuning of photoreceptors. Some species, however, have enhanced short-wavelength sensitivity, which probably helps with the detection of signals rich in ultraviolet and short wavelengths. In this study, we examined the visual system of Tiliqua rugosa, which has an ultraviolet/blue tongue, to gain insight into this species' visual ecology. We used electroretinograms, opsin sequencing and immunohistochemical labelling to characterize whole-eye spectral sensitivity and the elements that shape it. Our findings reveal that T. rugosa expresses all five opsins typically found in lizards (SWS1, SWS2, RH1, RH2 and LWS) but possesses greatly enhanced short-wavelength sensitivity compared with other diurnal lizards. This enhanced short-wavelength sensitivity is characterized by a broadening of the spectral sensitivity curve of the eye towards shorter wavelengths while the peak sensitivity of the eye at longer wavelengths (560 nm) remains similar to that of other diurnal lizards. While an increased abundance of SWS1 photoreceptors is thought to mediate elevated ultraviolet sensitivity in a couple of other lizard species, SWS1 photoreceptor abundance remains low in this species. Instead, our findings suggest that short-wavelength sensitivity is driven by multiple factors which include a potentially red-shifted SWS1 photoreceptor and the absence of short-wavelength-absorbing oil droplets. Examining the coincidence of enhanced short-wavelength sensitivity with blue tongues among lizards of this genus will provide further insight into the co-evolution of conspecific signals and whole-eye spectral sensitivity.
Publisher: The Royal Society
Date: 13-07-2016
Abstract: A comprehensive description of the spectral characteristics of retinal photoreceptors in palaeognaths is lacking. Moreover, controversy exists with respect to the spectral sensitivity of the short-wavelength-sensitive-1 (SWS1) opsin-based visual pigment expressed in one type of single cone: previous microspectrophotometric (MSP) measurements in the ostrich ( Struthio camelus ) suggested a violet-sensitive (VS) SWS1 pigment, but all palaeognath SWS1 opsin sequences obtained to date (including the ostrich) imply that the visual pigment is ultraviolet-sensitive (UVS). In this study, MSP was used to measure the spectral properties of visual pigments and oil droplets in the retinal photoreceptors of the emu ( Dromaius novaehollandiae ). Results show that the emu resembles most other bird species in possessing four spectrally distinct single cones, as well as double cones and rods. Four cone and a single rod opsin are expressed, each an orthologue of a previously identified pigment. The SWS1 pigment is clearly UVS (wavelength of maximum absorbance [ λ max ] = 376 nm), with key tuning sites (Phe86 and Cys90) consistent with other vertebrate UVS SWS1 pigments. Palaeognaths would appear, therefore, to have UVS SWS1 pigments. As they are considered to be basal in avian evolution, this suggests that UVS is the most likely ancestral state for birds. The functional significance of a dedicated UVS cone type in the emu is discussed.
Publisher: Society for Neuroscience
Date: 2019
DOI: 10.1523/ENEURO.0032-19.2019
Abstract: Mutations in the KCNV2 gene, which encodes the voltage-gated K + channel protein Kv8.2, cause a distinctive form of cone dystrophy with a supernormal rod response (CDSRR). Kv8.2 channel subunits only form functional channels when combined in a heterotetramer with Kv2.1 subunits encoded by the KCNB1 gene. The CDSRR disease phenotype indicates that photoreceptor adaptation is disrupted. The electroretinogram (ERG) response of affected in iduals shows depressed rod and cone activity, but what distinguishes this disease is the supernormal rod response to a bright flash of light. Here, we have utilized knock-out mutations of both genes in the mouse to study the pathophysiology of CDSRR. The Kv8.2 knock-out (KO) mice show many similarities to the human disorder, including a depressed a-wave and an elevated b-wave response with bright light stimulation. Optical coherence tomography (OCT) imaging and immunohistochemistry indicate that the changes in six-month-old Kv8.2 KO retinae are largely limited to the outer nuclear layer (ONL), while outer segments appear intact. In addition, there is a significant increase in TUNEL - positive cells throughout the retina. The Kv2.1 KO and double KO mice also show a severely depressed a-wave, but the elevated b-wave response is absent. Interestingly, in all three KO genotypes, the c-wave is totally absent. The differential response shown here of these KO lines, that either possess homomeric channels or lack channels completely, has provided further insights into the role of K + channels in the generation of the a-, b-, and c-wave components of the ERG.
No related grants have been discovered for Jessica Mountford.