Vilaiwan Fernandes - Academia.edu (original) (raw)
Papers by Vilaiwan Fernandes
Frontiers in Cell and Developmental Biology
Glial cells are an essential component of the nervous system of vertebrates and invertebrates. In... more Glial cells are an essential component of the nervous system of vertebrates and invertebrates. In the human brain, glia are as numerous as neurons, yet the importance of glia to nearly every aspect of nervous system development has only been expounded over the last several decades. Glia are now known to regulate neural specification, synaptogenesis, synapse function, and even broad circuit function. Given their ubiquity, it is not surprising that the contribution of glia to neuronal disease pathogenesis is a growing area of research. In this review, we will summarize the accumulated evidence of glial participation in several distinct phases of nervous system development and organization—neural specification, circuit wiring, and circuit function. Finally, we will highlight how these early developmental roles of glia contribute to nervous system dysfunction in neurodevelopmental and neurodegenerative disorders.
Time-lapse imaging is an essential tool to study dynamic biological processes that cannot be disc... more Time-lapse imaging is an essential tool to study dynamic biological processes that cannot be discerned from fixed samples alone. However, imaging cell- and tissue-level processes in intact animals poses numerous challenges if the organism is opaque and/or motile. Explant cultures of intact tissues circumvent some of these challenges, but sample drift remains a considerable obstacle. We employed a simple yet effective technique to immobilize tissues in medium-bathed agarose. We applied this technique to study multiple Drosophila tissues from first-instar larvae to adult stages in various orientations and with no evidence of anisotropic pressure or stress damage. Using this method, we were able to image fine features for up to 18 hours and make novel observations. Specifically, we report that fibers characteristic of quiescent neuroblasts are inherited by their basal daughters during reactivation; that the lamina in the developing visual system is assembled roughly 2-3 columns at a ti...
Science (New York, N.Y.), 2017
Neuronal birth and specification must be coordinated across the developing brain to generate the ... more Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia. In response to photoreceptor-EGF, glia produce insulin-like peptides, which induce lamina neuronal differentiation. Our study identifies a role for glia in coordinating neuronal development across distinct brain regions, thus reconciling the timing of column assembly with that of delayed differentiation, as well as the spatiotemporal pattern of lamina neuron differentiation.
Current opinion in neurobiology, 2017
During development a limited number of progenitors generate diverse cell types that comprise the ... more During development a limited number of progenitors generate diverse cell types that comprise the nervous system. Neuronal diversity, which arises largely at the level of neural stem cells, is critical for brain function. Often these cells exhibit temporal patterning: they sequentially produce neurons of distinct cell fates as a consequence of intrinsic and/or extrinsic cues. Here, we review recent advances in temporal patterning during neuronal specification, focusing on conserved players and mechanisms in invertebrate and vertebrate models. These studies underscore temporal patterning as an evolutionarily conserved strategy to generate neuronal diversity. Understanding the general principles governing temporal patterning and the molecular players involved will improve our ability to direct neural progenitors towards specific neuronal fates for brain repair.
Journal of Experimental Neuroscience
Various regions of the developing brain coordinate their construction so that the correct types a... more Various regions of the developing brain coordinate their construction so that the correct types and numbers of cells are generated to build a functional network. We previously discovered that wrapping glia in the Drosophila visual system are essential for coordinating retinal and lamina development. We showed that wrapping glia, which ensheath photoreceptor axons, respond to an epidermal growth factor cue from photoreceptors by secreting insulins. Wrapping glial insulins activate the mitogen-activated protein kinase (MAPK) pathway downstream of insulin receptor in lamina precursors to induce neuronal differentiation. The signaling relay via wrapping glia introduces a delay that allows the lamina to assemble the correct stoichiometry and physical alignment of precursors before differentiating and imposes a stereotyped spatiotemporal pattern that is relevant for specifying the individual lamina neuron fates. Here, we further describe how wrapping glia morphogenesis correlates with the timing of lamina neuron differentiation by 2-photon live imaging. We also show that although MAPK activity in lamina precursors drives neuronal differentiation, the upstream receptor driving MAPK activation in lamina precursors and the ligand secreted by wrapping glia to trigger it differentially affect lamina neuron differentiation. These results highlight differences in MAPK signaling properties and confirm that communication between photoreceptors, wrapping glia, and lamina precursors must be precisely controlled to build a complex neural network.
Cell Reports, 2016
How neuronal and glial fates are specified from neural precursor cells is an important question f... more How neuronal and glial fates are specified from neural precursor cells is an important question for developmental neurobiologists. We address this question in the Drosophila optic lobe, composed of the lamina, medulla, and lobula complex. We show that two gliogenic regions posterior to the prospective lamina also produce lamina wide-field (Lawf) neurons, which share common progenitors with lamina glia. These progenitors express neither canonical neuroblast nor lamina precursor cell markers. They bifurcate into two sub-lineages in response to Notch signaling, generating lamina glia or Lawf neurons, respectively. The newly born glia and Lawfs then migrate tangentially over substantial distances to reach their target tissue. Thus, Lawf neurogenesis, which includes a common origin with glia, as well as neuronal migration, resembles several aspects of vertebrate neurogenesis.
Developmental biology, Jan 4, 2015
Generating cellular heterogeneity is crucial to the development of complex organs. Organ-fate sel... more Generating cellular heterogeneity is crucial to the development of complex organs. Organ-fate selector genes and signalling pathways generate cellular diversity by subdividing and patterning naïve tissues to assign them regional identities. The Drosophila eye-antennal imaginal disc is a well-characterised system in which to study regional specification as it is first divided into antennal and eye fates and subsequently retinal differentiation occurs within only the eye field. During development, signalling pathways and selector genes compete with and mutually antagonize each other to subdivide the tissue. Wingless (Wg) signalling is the main inhibitor of retinal differentiation; it does so by promoting antennal/ head-fate via selector factors and by antagonizing Hedgehog (Hh), the principal differentiation-initiating signal. Wg signalling must be suppressed by JAK/STAT at the disc posterior in order to initiate retinal differentiation. Ras/MEK/MAPK signalling has also been implicate...
Developmental Biology, 2014
Proceedings of the National Academy of Sciences, 2011
Ants are some of the most abundant and familiar animals on Earth, and they play vital roles in mo... more Ants are some of the most abundant and familiar animals on Earth, and they play vital roles in most terrestrial ecosystems. Although all ants are eusocial, and display a variety of complex and fascinating behaviors, few genomic resources exist for them. Here, we report the draft genome sequence of a particularly widespread and well-studied species, the invasive Argentine ant (Linepithema humile), which was accomplished using a combination of 454 (Roche) and Illumina sequencing and community-based funding rather than federal grant support. Manual annotation of >1,000 genes from a variety of different gene families and functional classes reveals unique features of the Argentine…
Proceedings of the National Academy of Sciences, 2011
We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome w... more We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in GC content and compositional organization, and possesses a complete CpG methylation toolkit, its predicted genomic CpG content differs markedly from the other hymenopterans. Gene networks involved in generating key differences between the queen and worker castes (e.g., wings and ovaries) show signatures of increased methylation and suggest that ants and bees may have independently co-opted the same gene regulatory mechanisms for reproductive division of labor. Gene family expansions (e.g., 344 functional odorant receptors) and pseudogene accumulation in chemoreception and P450 genes compared with A. mellifera and N. vitripennis are consistent with major life-history changes during the adaptive radiation of Pogonomyrmex spp., perhaps in parallel with the development of the North American deserts.
PLoS Computational Biology, 2009
Many genetic networks are astonishingly robust to quantitative variation, allowing these networks... more Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through ''survival of the compatible'': those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles.
Frontiers in Cell and Developmental Biology
Glial cells are an essential component of the nervous system of vertebrates and invertebrates. In... more Glial cells are an essential component of the nervous system of vertebrates and invertebrates. In the human brain, glia are as numerous as neurons, yet the importance of glia to nearly every aspect of nervous system development has only been expounded over the last several decades. Glia are now known to regulate neural specification, synaptogenesis, synapse function, and even broad circuit function. Given their ubiquity, it is not surprising that the contribution of glia to neuronal disease pathogenesis is a growing area of research. In this review, we will summarize the accumulated evidence of glial participation in several distinct phases of nervous system development and organization—neural specification, circuit wiring, and circuit function. Finally, we will highlight how these early developmental roles of glia contribute to nervous system dysfunction in neurodevelopmental and neurodegenerative disorders.
Time-lapse imaging is an essential tool to study dynamic biological processes that cannot be disc... more Time-lapse imaging is an essential tool to study dynamic biological processes that cannot be discerned from fixed samples alone. However, imaging cell- and tissue-level processes in intact animals poses numerous challenges if the organism is opaque and/or motile. Explant cultures of intact tissues circumvent some of these challenges, but sample drift remains a considerable obstacle. We employed a simple yet effective technique to immobilize tissues in medium-bathed agarose. We applied this technique to study multiple Drosophila tissues from first-instar larvae to adult stages in various orientations and with no evidence of anisotropic pressure or stress damage. Using this method, we were able to image fine features for up to 18 hours and make novel observations. Specifically, we report that fibers characteristic of quiescent neuroblasts are inherited by their basal daughters during reactivation; that the lamina in the developing visual system is assembled roughly 2-3 columns at a ti...
Science (New York, N.Y.), 2017
Neuronal birth and specification must be coordinated across the developing brain to generate the ... more Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia. In response to photoreceptor-EGF, glia produce insulin-like peptides, which induce lamina neuronal differentiation. Our study identifies a role for glia in coordinating neuronal development across distinct brain regions, thus reconciling the timing of column assembly with that of delayed differentiation, as well as the spatiotemporal pattern of lamina neuron differentiation.
Current opinion in neurobiology, 2017
During development a limited number of progenitors generate diverse cell types that comprise the ... more During development a limited number of progenitors generate diverse cell types that comprise the nervous system. Neuronal diversity, which arises largely at the level of neural stem cells, is critical for brain function. Often these cells exhibit temporal patterning: they sequentially produce neurons of distinct cell fates as a consequence of intrinsic and/or extrinsic cues. Here, we review recent advances in temporal patterning during neuronal specification, focusing on conserved players and mechanisms in invertebrate and vertebrate models. These studies underscore temporal patterning as an evolutionarily conserved strategy to generate neuronal diversity. Understanding the general principles governing temporal patterning and the molecular players involved will improve our ability to direct neural progenitors towards specific neuronal fates for brain repair.
Journal of Experimental Neuroscience
Various regions of the developing brain coordinate their construction so that the correct types a... more Various regions of the developing brain coordinate their construction so that the correct types and numbers of cells are generated to build a functional network. We previously discovered that wrapping glia in the Drosophila visual system are essential for coordinating retinal and lamina development. We showed that wrapping glia, which ensheath photoreceptor axons, respond to an epidermal growth factor cue from photoreceptors by secreting insulins. Wrapping glial insulins activate the mitogen-activated protein kinase (MAPK) pathway downstream of insulin receptor in lamina precursors to induce neuronal differentiation. The signaling relay via wrapping glia introduces a delay that allows the lamina to assemble the correct stoichiometry and physical alignment of precursors before differentiating and imposes a stereotyped spatiotemporal pattern that is relevant for specifying the individual lamina neuron fates. Here, we further describe how wrapping glia morphogenesis correlates with the timing of lamina neuron differentiation by 2-photon live imaging. We also show that although MAPK activity in lamina precursors drives neuronal differentiation, the upstream receptor driving MAPK activation in lamina precursors and the ligand secreted by wrapping glia to trigger it differentially affect lamina neuron differentiation. These results highlight differences in MAPK signaling properties and confirm that communication between photoreceptors, wrapping glia, and lamina precursors must be precisely controlled to build a complex neural network.
Cell Reports, 2016
How neuronal and glial fates are specified from neural precursor cells is an important question f... more How neuronal and glial fates are specified from neural precursor cells is an important question for developmental neurobiologists. We address this question in the Drosophila optic lobe, composed of the lamina, medulla, and lobula complex. We show that two gliogenic regions posterior to the prospective lamina also produce lamina wide-field (Lawf) neurons, which share common progenitors with lamina glia. These progenitors express neither canonical neuroblast nor lamina precursor cell markers. They bifurcate into two sub-lineages in response to Notch signaling, generating lamina glia or Lawf neurons, respectively. The newly born glia and Lawfs then migrate tangentially over substantial distances to reach their target tissue. Thus, Lawf neurogenesis, which includes a common origin with glia, as well as neuronal migration, resembles several aspects of vertebrate neurogenesis.
Developmental biology, Jan 4, 2015
Generating cellular heterogeneity is crucial to the development of complex organs. Organ-fate sel... more Generating cellular heterogeneity is crucial to the development of complex organs. Organ-fate selector genes and signalling pathways generate cellular diversity by subdividing and patterning naïve tissues to assign them regional identities. The Drosophila eye-antennal imaginal disc is a well-characterised system in which to study regional specification as it is first divided into antennal and eye fates and subsequently retinal differentiation occurs within only the eye field. During development, signalling pathways and selector genes compete with and mutually antagonize each other to subdivide the tissue. Wingless (Wg) signalling is the main inhibitor of retinal differentiation; it does so by promoting antennal/ head-fate via selector factors and by antagonizing Hedgehog (Hh), the principal differentiation-initiating signal. Wg signalling must be suppressed by JAK/STAT at the disc posterior in order to initiate retinal differentiation. Ras/MEK/MAPK signalling has also been implicate...
Developmental Biology, 2014
Proceedings of the National Academy of Sciences, 2011
Ants are some of the most abundant and familiar animals on Earth, and they play vital roles in mo... more Ants are some of the most abundant and familiar animals on Earth, and they play vital roles in most terrestrial ecosystems. Although all ants are eusocial, and display a variety of complex and fascinating behaviors, few genomic resources exist for them. Here, we report the draft genome sequence of a particularly widespread and well-studied species, the invasive Argentine ant (Linepithema humile), which was accomplished using a combination of 454 (Roche) and Illumina sequencing and community-based funding rather than federal grant support. Manual annotation of >1,000 genes from a variety of different gene families and functional classes reveals unique features of the Argentine…
Proceedings of the National Academy of Sciences, 2011
We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome w... more We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in GC content and compositional organization, and possesses a complete CpG methylation toolkit, its predicted genomic CpG content differs markedly from the other hymenopterans. Gene networks involved in generating key differences between the queen and worker castes (e.g., wings and ovaries) show signatures of increased methylation and suggest that ants and bees may have independently co-opted the same gene regulatory mechanisms for reproductive division of labor. Gene family expansions (e.g., 344 functional odorant receptors) and pseudogene accumulation in chemoreception and P450 genes compared with A. mellifera and N. vitripennis are consistent with major life-history changes during the adaptive radiation of Pogonomyrmex spp., perhaps in parallel with the development of the North American deserts.
PLoS Computational Biology, 2009
Many genetic networks are astonishingly robust to quantitative variation, allowing these networks... more Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through ''survival of the compatible'': those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles.