The Experts below are selected from a list of 2109 Experts worldwide ranked by ideXlab platform
Ralf Stanewsky - One of the best experts on this subject based on the ideXlab platform.
-
light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock
Current Biology, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:Summary The daily changes of light and dark exemplify a prominent cue for the synchronization of circadian clocks with the environment. The match between external and internal time is crucial for the fitness of organisms, and desynchronization has been linked to numerous physical and mental health problems. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila, both the Visual system and non-image-forming photoreceptors contribute to circadian clock resetting. In Drosophila, light-dependent degradation of the clock protein TIMELESS by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. To better understand the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. In this variant, the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular light synchronization. This function depends on an alternative phospholipase C-β enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting. We show that this pathway requires the ubiquitin ligase CULLIN-3, possibly mediating CRY-independent degradation of TIMELESS during light:dark cycles. Our results suggest that the PLC21C-mediated contribution to circadian clock entrainment operates on a drastically slower timescale compared with fast, norpA-dependent Visual Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (h) in order to reliably synchronize their internal clocks with the external time.
-
less is more light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock in the absence of cryptochrome
bioRxiv, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila both the Visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. In order to understand the nature of the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. We show that in this variant the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-Beta enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that Visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, Visual and image forming Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.
-
non canonical Phototransduction mediates synchronization of the drosophila melanogaster circadian clock and retinal light responses
Current Biology, 2018Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the Visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical Visual Rhodopsin Phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical Visual Phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye.
Ignacio Fernandez - One of the best experts on this subject based on the ideXlab platform.
-
warfarin exposed zebrafish embryos resembles human warfarin embryopathy in a dose and developmental time dependent manner from molecular mechanisms to environmental concerns
Ecotoxicology and Environmental Safety, 2019Co-Authors: Luis Granadeiro, Ron P Dirks, Juan B Ortizdelgado, Paulo J Gavaia, Carmen Sarasquete, Vincent Laize, Leonor M Cancela, Ignacio FernandezAbstract:Abstract Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly overrepresented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, Visual Phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.
-
Warfarin-exposed zebrafish embryos resembles human warfarin embryopathy in a dose and developmental-time dependent manner - From molecular mechanisms to environmental concerns
'Elsevier BV', 2019Co-Authors: Granadeiro Luis, Dirks, Ron P., Ortiz-delgado, Juan B., Gavaia J. Paulo, Sarasquete Carmen, Laizé Vincent, Leonor Cancela M., Ignacio FernandezAbstract:Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly over-represented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, Visual Phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.Portuguese Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019]project MET2VI - Ministerio de Ciencia, Innovacion y Universidades of the Spanish Government [RTI2018-099029-A-I00]info:eu-repo/semantics/publishedVersio
Maite Ogueta - One of the best experts on this subject based on the ideXlab platform.
-
light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock
Current Biology, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:Summary The daily changes of light and dark exemplify a prominent cue for the synchronization of circadian clocks with the environment. The match between external and internal time is crucial for the fitness of organisms, and desynchronization has been linked to numerous physical and mental health problems. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila, both the Visual system and non-image-forming photoreceptors contribute to circadian clock resetting. In Drosophila, light-dependent degradation of the clock protein TIMELESS by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. To better understand the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. In this variant, the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular light synchronization. This function depends on an alternative phospholipase C-β enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting. We show that this pathway requires the ubiquitin ligase CULLIN-3, possibly mediating CRY-independent degradation of TIMELESS during light:dark cycles. Our results suggest that the PLC21C-mediated contribution to circadian clock entrainment operates on a drastically slower timescale compared with fast, norpA-dependent Visual Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (h) in order to reliably synchronize their internal clocks with the external time.
-
less is more light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock in the absence of cryptochrome
bioRxiv, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila both the Visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. In order to understand the nature of the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. We show that in this variant the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-Beta enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that Visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, Visual and image forming Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.
-
non canonical Phototransduction mediates synchronization of the drosophila melanogaster circadian clock and retinal light responses
Current Biology, 2018Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the Visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical Visual Rhodopsin Phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical Visual Phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye.
Roger C Hardie - One of the best experts on this subject based on the ideXlab platform.
-
light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock
Current Biology, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:Summary The daily changes of light and dark exemplify a prominent cue for the synchronization of circadian clocks with the environment. The match between external and internal time is crucial for the fitness of organisms, and desynchronization has been linked to numerous physical and mental health problems. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila, both the Visual system and non-image-forming photoreceptors contribute to circadian clock resetting. In Drosophila, light-dependent degradation of the clock protein TIMELESS by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. To better understand the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. In this variant, the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular light synchronization. This function depends on an alternative phospholipase C-β enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting. We show that this pathway requires the ubiquitin ligase CULLIN-3, possibly mediating CRY-independent degradation of TIMELESS during light:dark cycles. Our results suggest that the PLC21C-mediated contribution to circadian clock entrainment operates on a drastically slower timescale compared with fast, norpA-dependent Visual Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (h) in order to reliably synchronize their internal clocks with the external time.
-
less is more light sampling via throttled Visual Phototransduction robustly synchronizes the drosophila circadian clock in the absence of cryptochrome
bioRxiv, 2020Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila both the Visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the Visual system also contributes. In order to understand the nature of the Visual system contribution, we generated a genetic variant exhibiting extremely slow Phototransduction kinetics, yet normal sensitivity. We show that in this variant the Visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-Beta enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that Visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, Visual and image forming Phototransduction. Our findings are therefore consistent with the general idea that the Visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.
-
non canonical Phototransduction mediates synchronization of the drosophila melanogaster circadian clock and retinal light responses
Current Biology, 2018Co-Authors: Maite Ogueta, Roger C Hardie, Ralf StanewskyAbstract:The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the Visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical Visual Rhodopsin Phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical Visual Phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye.
Luis Granadeiro - One of the best experts on this subject based on the ideXlab platform.
-
warfarin exposed zebrafish embryos resembles human warfarin embryopathy in a dose and developmental time dependent manner from molecular mechanisms to environmental concerns
Ecotoxicology and Environmental Safety, 2019Co-Authors: Luis Granadeiro, Ron P Dirks, Juan B Ortizdelgado, Paulo J Gavaia, Carmen Sarasquete, Vincent Laize, Leonor M Cancela, Ignacio FernandezAbstract:Abstract Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly overrepresented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, Visual Phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.
