Pax6 in Collembola: Adaptive Evolution of Eye Regression.
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ABSTRACT:
SUBMITTER: Hou YN
PROVIDER: S-EPMC4746759 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Project description:BackgroundHow and why animals lose eyesight during adaptation to the dark and food-limited cave environment has puzzled biologists since the time of Darwin. More recently, several different adaptive hypotheses have been proposed to explain eye degeneration based on studies in the teleost Astyanax mexicanus, which consists of blind cave-dwelling (cavefish) and sighted surface-dwelling (surface fish) forms. One of these hypotheses is that eye regression is the result of indirect selection for constructive characters that are negatively linked to eye development through the pleiotropic effects of Sonic Hedgehog (SHH) signaling. However, subsequent genetic analyses suggested that other mechanisms also contribute to eye regression in Astyanax cavefish. Here, we introduce a new approach to this problem by investigating the phenotypic and genetic relationships between a suite of non-visual constructive traits and eye regression.ResultsUsing quantitative genetic analysis of crosses between surface fish, the Pachón cavefish population and their hybrid progeny, we show that the adaptive vibration attraction behavior (VAB) and its sensory receptors, superficial neuromasts (SN) specifically found within the cavefish eye orbit (EO), are genetically correlated with reduced eye size. The quantitative trait loci (QTL) for these three traits form two clusters of congruent or overlapping QTL on Astyanax linkage groups (LG) 2 and 17, but not at the shh locus on LG 13. Ablation of EO SN in cavefish demonstrated a major role for these sensory receptors in VAB expression. Furthermore, experimental induction of eye regression in surface fish via shh overexpression showed that the absence of eyes was insufficient to promote the appearance of VAB or EO SN.ConclusionsWe conclude that natural selection for the enhancement of VAB and EO SN indirectly promotes eye regression in the Pachón cavefish population through an antagonistic relationship involving genetic linkage or pleiotropy among the genetic factors underlying these traits. This study demonstrates a trade-off between the evolution of a non-visual sensory system and eye regression during the adaptive evolution of Astyanax to the cave environment.
| S-EPMC3565949 | biostudies-literature
Project description:Regression analysis using line equations has been broadly applied in studying the evolutionary relationship between the response trait and its covariates. However, the characteristics among closely related species in nature present abundant diversities where the nonlinear relationship between traits have been frequently observed. By treating the evolution of quantitative traits along a phylogenetic tree as a set of continuous stochastic variables, statistical models for describing the dynamics of the optimum of the response trait and its covariates are built herein. Analytical representations for the response trait variables, as well as their optima among a group of related species, are derived. Due to the models' lack of tractable likelihood, a procedure that implements the Approximate Bayesian Computation (ABC) technique is applied for statistical inference. Simulation results show that the new models perform well where the posterior means of the parameters are close to the true parameters. Empirical analysis supports the new models when analyzing the trait relationship among kangaroo species.
| S-EPMC7916804 | biostudies-literature
Project description:Big data can easily be contaminated by outliers or contain variables with heavy-tailed distributions, which makes many conventional methods inadequate. To address this challenge, we propose the adaptive Huber regression for robust estimation and inference. The key observation is that the robustification parameter should adapt to the sample size, dimension and moments for optimal tradeoff between bias and robustness. Our theoretical framework deals with heavy-tailed distributions with bounded (1 + δ)-th moment for any δ > 0. We establish a sharp phase transition for robust estimation of regression parameters in both low and high dimensions: when δ ≥ 1, the estimator admits a sub-Gaussian-type deviation bound without sub-Gaussian assumptions on the data, while only a slower rate is available in the regime 0 < δ < 1 and the transition is smooth and optimal. In addition, we extend the methodology to allow both heavy-tailed predictors and observation noise. Simulation studies lend further support to the theory. In a genetic study of cancer cell lines that exhibit heavy-tailedness, the proposed methods are shown to be more robust and predictive.
| S-EPMC7603940 | biostudies-literature
Project description:A Saccharomyces cerevisiae population was cultured for many generations under conditions to which it is not optimally adapted. These experiments were designed to investigate adaptive evolution under natural selection. This study is described in more detail in Ferea TL, et al. 1999. Proc Natl Acad Sci USA 96:9721-6
2002-02-11 | E-GEOD-29 | biostudies-arrayexpress
Project description:The transcription factor Pax6 is considered the master control gene for eye formation because (1) it is present within the genomes and retina/lens of all animals with a visual system; (2) severe retinal defects accompany its loss; (3) Pax6 genes have the ability to substitute for one another across the animal kingdom; and (4) Pax6 genes are capable of inducing ectopic eye/lens in flies and mammals. Many roles of Pax6 were first elucidated in Drosophila through studies of the gene eyeless (ey), which controls both growth of the entire eye-antennal imaginal disc and fate specification of the eye. We show that Ey also plays a surprising role within cells of the peripodial epithelium to control pattern formation. It regulates the expression of decapentaplegic (dpp), which is required for initiation of the morphogenetic furrow in the eye itself. Loss of Ey within the peripodial epithelium leads to the loss of dpp expression within the eye, failure of the furrow to initiate, and abrogation of retinal development. These findings reveal an unexpected mechanism for how Pax6 controls eye development in Drosophila.
| S-EPMC6110151 | biostudies-literature
Project description:PurposeThe purpose of this study was to elucidate the role and molecular consequences of impaired glutathione (GSH) biosynthesis on eye development.MethodsGSH biosynthesis was impaired in surface ectoderm-derived ocular tissues by crossing Gclcf/f mice with hemizygous Le-Cre transgenic mice to produce Gclcf/f/Le-CreTg/- (KO) mice. Control mice included Gclcf/fand Gclcwt/wt/Le-CreTg/- mice (CRE). Eyes from all mice (at various stages of eye development) were subjected to histological, immunohistochemical, Western blot, RT-qPCR, RNA-seq, and subsequent Gene Ontology, Ingenuity Pathway Analysis and TRANSFAC analyses. PAX6 transactivation activity was studied using a luciferase reporter assay in HEK293T cells depleted of GSH using buthionine sulfoximine (BSO).ResultsDeletion of Gclc diminished GSH levels, increased reactive oxygen species (ROS), and caused an overt microphthalmia phenotype characterized by malformation of the cornea, iris, lens, and retina that is distinct from and much more profound than the one observed in CRE mice. In addition, only the lenses of KO mice displayed reduced crystallin (α, β), PITX3 and Foxe3 expression. RNA-seq analyses at postnatal day 1 revealed 1552 differentially expressed genes (DEGs) in the lenses of KO mice relative to those from Gclcf/f mice, with Crystallin and lens fiber cell identity genes being downregulated while lens epithelial cell identity and immune response genes were upregulated. Bioinformatic analysis of the DEGs implicated PAX6 as a key upstream regulator. PAX6 transactivation activity was impaired in BSO-treated HEK293T cells.ConclusionsThese data suggest that impaired ocular GSH biosynthesis may disrupt eye development and PAX6 function.
| S-EPMC8560581 | biostudies-literature
Project description:Glutathione (GSH) is a critical endogenous antioxidant that protects against intracellular oxidative stress. As such, pathological alterations in GSH levels are linked to a myriad of diseases including cancer, neurodegeneration and cataract. The rate limiting step in GSH biosynthesis is catalyzed by the glutamate cysteine ligase catalytic subunit (GCLC). The high expression of GCLC in the lens supports the synthesis of millimolar concentrations of GSH in this tissue. Herein, we describe the morphological consequences of deleting (knocking out) Gclc from surface ectoderm-derived ocular tissues (using the Le-Cre transgene; Gclc KO) which includes an overt microphthalmia phenotype and severely disrupted formation of multiple ocular structures (i.e., cornea, iris, lens, retina). Controlling for the Le-Cre transgene revealed that the deletion of Gclc significantly exacerbated the microphthalmia phenotype in Le-Cre hemizygous mice and resulted in dysregulated gene expression that was unique to only the lenses of KO mice. We further characterized the impaired lens development by conducting an RNA-seq experiment on KO and Gclc control (CON) mouse lens at the day of birth. RNA-sequencing revealed significant differences between Gclc knockout (KO) and Gclc control (CON) lenses, including down-regulation of crystallins and lens fiber cell identity genes, and up-regulation of lens epithelial cell identity genes. In addition, genes related to the immune system (e.g., immune system process, inflammatory response, neutrophil chemotaxis) were upregulated, and genes related to eye/lens development were downregulated. TRANSFAC analysis of differentially expressed genes (DEGs) in the lens of Gclc KO mice implicated PAX6 as a key upstream regulator of Gclc KO sensitive genes. This was further supported by a strong positive correlation between the transcriptomes of the lenses of Gclc KO and Pax6 KO mice. Strikingly, the dysregulation of PAX6-regulated genes in Gclc KO mice was observed despite no change in the ocular localization of PAX6 or decrease in the expression of PAX6 in the lens. In vitro experiments demonstrated that suppression of intracellular GSH concentrations resulted in impairment of PAX6 transactivation activity. Taken together, the present results elucidate a novel mechanism wherein intracellular GSH concentrations may modulate PAX6 activity.
2021-08-23 | GSE175394 | GEO
Project description:We propose a new method for regression using a parsimonious and scientifically interpretable representation of functional predictors. Our approach is designed for data that exhibit features such as spikes, dips, and plateaus whose frequency, location, size, and shape varies stochastically across subjects. We propose Bayesian inference of the joint functional and exposure models, and give a method for efficient computation. We contrast our approach with existing state-of-the-art methods for regression with functional predictors, and show that our method is more effective and efficient for data that include features occurring at varying locations. We apply our methodology to a large and complex dataset from the Sleep Heart Health Study, to quantify the association between sleep characteristics and health outcomes. Software and technical appendices are provided in online supplemental materials.
| S-EPMC3842620 | biostudies-literature
Project description:Going Wireless: Fe(III) Oxide Reduction without Pili by Geobacter sulfurreducens Strain JS-1
| PRJEB4547 | ENA
Project description:PURPOSE:To analyze the effects of Pax6 overexpression and its interaction with genetic background on eye development. METHODS:Histologic features of eyes from hemizygous PAX77(+/-) transgenic (high Pax6 gene dose) and wild-type mice were compared on different genetic backgrounds. Experimental PAX77(+/-)<-->wild-type and control wild-type<-->wild-type chimeras were analyzed to investigate the causes of abnormal eye development in PAX77(+/-) mice. RESULTS:PAX77(+/-) mice showed an overlapping but distinct spectrum of eye abnormalities to Pax6(+/-) heterozygotes (low Pax6 dose). Some previously reported PAX77(+/-) eye abnormalities did not occur on all three genetic backgrounds examined. Several types of eye abnormalities occurred in the experimental PAX77(+/-)<-->wild-type chimeras, and they occurred more frequently in chimeras with higher contributions of PAX77(+/-) cells. Groups of RPE cells intruded into the optic nerve sheath, indicating that the boundary between the retina and optic nerve may be displaced. Both PAX77(+/-) and wild-type cells were involved in this ingression and in retinal folds, suggesting that neither effect was cell-autonomous. Cell-autonomous effects included failure of PAX77(+/-) and wild-type cells to mix normally and overrepresentation of PAX77(+/-) in the lens epithelium and RPE. CONCLUSIONS:The extent of PAX77(+/-) eye abnormalities depended on PAX77(+/-) genotype, genetic background, and stochastic variation. Chimera analysis identified two types of cell-autonomous effects of the PAX77(+/-) genotype. Abnormal cell mixing between PAX77(+/-) and wild-type cells suggests altered expression of cell surface adhesion molecules. Some phenotypic differences between PAX77(+/-)<-->wild-type and Pax6(+/-)<-->wild-type chimeras may reflect differences in the levels of PAX77(+/-) and Pax6(+/-) contributions to chimeric lenses.
| S-EPMC2763115 | biostudies-literature