scholarly journals Eye morphogenesis in the blind Mexican cavefish

Biology Open ◽  
2021 ◽  
Author(s):  
Lucie Devos ◽  
François Agnès ◽  
Joanne Edouard ◽  
Victor Simon ◽  
Laurent Legendre ◽  
...  
Keyword(s):  
Morphological Evolution ◽  
Developmental Defects ◽  
Cell Behaviors ◽  
Astyanax Mexicanus ◽  
Cellular Processes ◽  
Gfp Reporter ◽  
Tightly Coupled ◽  
Vertebrate Eye ◽  
Blind Cavefish ◽  
Type Specification

The morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Disturbances in these events can lead to developmental defects and blindness. Here, we have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified defects in migratory cell behaviors during evagination which participate in the reduced optic vesicle size in cavefish, without proliferation defect. Further, impaired optic cup invagination shifts the relative position of the lens and contributes to coloboma in cavefish. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.

scholarly journals Morphogenetic and patterning defects explain the coloboma phenotype of the eye in the Mexican cavefish

2019 ◽  
Author(s):  
Lucie Devos ◽  
Florent Klee ◽  
Joanne Edouard ◽  
Victor Simon ◽  
Laurent Legendre ◽  
...  
Keyword(s):  
Morphological Evolution ◽  
Developmental Defects ◽  
Optic Stalk ◽  
Astyanax Mexicanus ◽  
Cellular Processes ◽  
Tightly Coupled ◽  
Vertebrate Eye ◽  
Blind Cavefish ◽  
Epithelium Cells ◽  
Type Specification

AbstractThe morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Any disturbance in these events can lead to developmental defects and blindness. Here we have deciphered the sequence of defective events leading to coloboma phenotype in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified major defects in initial optic vesicle size and optic cup invagination in cavefish. Combining these results with gene expression analyses, we also discovered defects in axial patterning affecting mainly the temporal retina, in optic stalk tissue specification, and in the spreading processes involving the retinal pigmented epithelium cells. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.

scholarly journals Gene flow and population structure in the Mexican blind cavefish complex (Astyanax mexicanus)

2012 ◽  
Vol 12 (1) ◽  
pp. 9 ◽  
Author(s):  
Martina Bradic ◽  
Peter Beerli ◽  
Francisco J García-de León ◽  
Sarai Esquivel-Bobadilla ◽  
Richard L Borowsky
Keyword(s):  
Population Structure ◽  
Gene Flow ◽  
Astyanax Mexicanus ◽  
Blind Cavefish

scholarly journals Survivin Loss in Thymocytes Triggers p53-mediated Growth Arrest and p53-independent Cell Death

2004 ◽  
Vol 199 (3) ◽  
pp. 399-410 ◽  
Author(s):  
Hitoshi Okada ◽  
Chris Bakal ◽  
Arda Shahinian ◽  
Andrew Elia ◽  
Andrew Wakeham ◽  
...  
Keyword(s):  
Cell Death ◽  
Critical Role ◽  
Cell Receptor ◽  
Thymocyte Development ◽  
Double Positive ◽  
Developmental Defects ◽  
Cycle Arrest ◽  
Tightly Coupled ◽  
Early Embryonic Stage ◽  
P53 Inactivation

Because survivin-null embryos die at an early embryonic stage, the role of survivin in thymocyte development is unknown. We have investigated the role by deleting the survivin gene only in the T lineage and show here that loss of survivin blocks the transition from CD4− CD8− double negative (DN) thymocytes to CD4+ CD8+ double positive cells. Although the pre–T cell receptor signaling pathway is intact in survivin-deficient thymocytes, the cells cannot respond to its signals. In response to proliferative stimuli, cycling survivin-deficient DN cells exhibit cell cycle arrest, a spindle formation defect, and increased cell death. Strikingly, loss of survivin activates the tumor suppressor p53. However, the developmental defects caused by survivin deficiency cannot be rescued by p53 inactivation or introduction of Bcl-2. These lines of evidence indicate that developing thymocytes depend on the cytoprotective function of survivin and that this function is tightly coupled to cell proliferation but independent of p53 and Bcl-2. Thus, survivin plays a critical role in early thymocyte development.

Modulation of cell behaviors by electrochemically active polyelectrolyte multilayers

e-Polymers ◽  
2014 ◽  
Vol 14 (5) ◽  
pp. 297-304
Author(s):  
Guo-xun Chang ◽  
Ke-feng Ren ◽  
Yi-xiu Zhao ◽  
Yi-xin Sun ◽  
Jian Ji
Keyword(s):  
Mechanical Properties ◽  
Chemical Properties ◽  
Fibroblast Cell ◽  
Electrochemical Treatment ◽  
Cell Behaviors ◽  
Cellular Processes ◽  
Tunable Mechanical Properties ◽  
And Migration ◽  
Nih 3T3 ◽  
Proliferation And Migration

AbstractIn addition to the topographical features and chemical properties of substrates, the mechanical properties are known as a vital regulator of cellular processes such as adhesion, proliferation, and migration, and have received considerable attention in recent years. In this work, electrochemical redox multilayers made of ferrocene-modified poly(ethylenimine) (PEI-Fc) and deoxyribonucleic acid (DNA) with controlled stiffness were used to investigate the effects of the mechanical properties of multilayers on fibroblast cell (NIH/3T3) behaviors. Redox PEI-Fc plays an essential role in inducing swelling in multilayers under an electrochemical stimulus, resulting in distinct changes in the stiffness of the multilayers. The Young’s modulus varied from 2.05 to 1.07 MPa for the (PEI-Fc/DNA) multilayers by changing the oxidation time of the electrochemical treatment. We demonstrated that the adhesion, proliferation, and migration of fibroblast cells depended on the multilayers’ stiffness. These results indicate that cell behaviors can be precisely controlled by electrochemical treatment, which provides a new way to prepare thin films with tunable mechanical properties with potential biomedical applications.

scholarly journals Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Andrew Beale ◽  
Christophe Guibal ◽  
T. Katherine Tamai ◽  
Linda Klotz ◽  
Sophie Cowen ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Astyanax Mexicanus ◽  
Blind Cavefish

scholarly journals Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

2021 ◽  
Author(s):  
Evan Lloyd ◽  
Brittnee McDole ◽  
Martin Privat ◽  
James B. Jaggard ◽  
Erik Duboué ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Neural Circuit ◽  
Astyanax Mexicanus ◽  
Evolutionary Selection ◽  
Environmental Perturbation ◽  
Multiple Components ◽  
Correlated Activity ◽  
Retinal Input ◽  
Hybrid Fish ◽  
Blind Cavefish

AbstractSensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.

scholarly journals Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yidi Sun ◽  
Nicole T Leong ◽  
Tommy Jiang ◽  
Astou Tangara ◽  
Xavier Darzacq ◽  
...  
Keyword(s):  
Quantitative Imaging ◽  
Threshold Level ◽  
Actin Assembly ◽  
Cellular Processes ◽  
Src Homology 3 ◽  
Filament Assembly ◽  
Tightly Coupled ◽  
Src Homology 3 Domain ◽  
Src Homology

Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. Quantitative imaging suggested that productive actin assembly initiation is tightly coupled to accumulation of threshold levels of WASP and WIP, but not to recruitment kinetics or release of autoinhibition. These studies provide evidence that WASP and WIP play central roles in establishment of a robust multivalent SH3 domain-PRM network in vivo, giving actin assembly onset at endocytic sites a switch-like behavior.

scholarly journals Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Thomas J. Ha ◽  
◽  
Peter G. Y. Zhang ◽  
Remi Robert ◽  
Joanna Yeung ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Regulators ◽  
Cell Types ◽  
Cerebellar Development ◽  
Developmental Defects ◽  
Cellular Processes ◽  
Functional Investigation ◽  
Level Of Understanding ◽  
Temporal Expression Pattern ◽  
Cap Analysis

Abstract Background The work of the FANTOM5 Consortium has brought forth a new level of understanding of the regulation of gene transcription and the cellular processes involved in creating diversity of cell types. In this study, we extended the analysis of the FANTOM5 Cap Analysis of Gene Expression (CAGE) transcriptome data to focus on understanding the genetic regulators involved in mouse cerebellar development. Results We used the HeliScopeCAGE library sequencing on cerebellar samples over 8 embryonic and 4 early postnatal times. This study showcases temporal expression pattern changes during cerebellar development. Through a bioinformatics analysis that focused on transcription factors, their promoters and binding sites, we identified genes that appear as strong candidates for involvement in cerebellar development. We selected several candidate transcriptional regulators for validation experiments including qRT-PCR and shRNA transcript knockdown. We observed marked and reproducible developmental defects in Atf4, Rfx3, and Scrt2 knockdown embryos, which support the role of these genes in cerebellar development. Conclusions The successful identification of these novel gene regulators in cerebellar development demonstrates that the FANTOM5 cerebellum time series is a high-quality transcriptome database for functional investigation of gene regulatory networks in cerebellar development.

scholarly journals p53 Activation in Genetic Disorders: Different Routes to the Same Destination

2021 ◽  
Vol 22 (17) ◽  
pp. 9307
Author(s):  
Yu-Young Tsai ◽  
Chun-Hao Su ◽  
Woan-Yuh Tarn
Keyword(s):  
Developmental Disorders ◽  
Genetic Disorders ◽  
Pleiotropic Effect ◽  
Telomere Maintenance ◽  
Tumor Suppressor P53 ◽  
Inherited Disorders ◽  
Developmental Defects ◽  
Cellular Processes ◽  
Damage Repair ◽  
P53 Activation

The tumor suppressor p53 is critical for preventing neoplastic transformation and tumor progression. Inappropriate activation of p53, however, has been observed in a number of human inherited disorders that most often affect development of the brain, craniofacial region, limb skeleton, and hematopoietic system. Genes related to these developmental disorders are essentially involved in transcriptional regulation/chromatin remodeling, rRNA metabolism, DNA damage-repair pathways, telomere maintenance, and centrosome biogenesis. Perturbation of these activities or cellular processes may result in p53 accumulation in cell cultures, animal models, and perhaps humans as well. Mouse models of several p53 activation-associated disorders essentially recapitulate human traits, and inactivation of p53 in these models can alleviate disorder-related phenotypes. In the present review, we focus on how dysfunction of the aforementioned biological processes causes developmental defects via excessive p53 activation. Notably, several disease-related genes exert a pleiotropic effect on those cellular processes, which may modulate the magnitude of p53 activation and establish or disrupt regulatory loops. Finally, we discuss potential therapeutic strategies for genetic disorders associated with p53 misactivation.

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