scholarly journals Variability of an early developmental cell population underlies stochastic laterality defects

2020 ◽  
Author(s):  
Roberto Moreno-Ayala ◽  
Pedro Olivares-Chauvet ◽  
Ronny Schäfer ◽  
Jan Philipp Junker
Keyword(s):  
Elevated Temperature ◽  
Maternal Effects ◽  
Genetic Background ◽  
Normal Development ◽  
Cell Number ◽  
Vertebrate Development ◽  
Stochastic Variation ◽  
Number Variation ◽  
Early Developmental ◽  
Laterality Defects

Embryonic development seemingly proceeds with almost perfect precision. However, it is largely unknown how much underlying microscopic variability is compatible with normal development. Here, we quantified embryo-to-embryo variability in vertebrate development, by studying cell number variation in the zebrafish endoderm. We noticed that the size of a sub- population of the endoderm, the dorsal forerunner cells (which later form the left-right organizer), exhibits significantly more embryo-to-embryo variation than the rest of the endoderm. We found that, when incubated at elevated temperature, the frequency of left-right laterality defects is increased drastically in embryos with a low number of dorsal forerunner cells. Furthermore, we observed that these fluctuations have a large stochastic component among fish of the same genetic background. Hence, a stochastic variation in early development leads to a remarkably strong macroscopic phenotype. These fluctuations appear to be associated with maternal effects in the specification of the dorsal forerunner cells.

A quantitative study of the growth and development of the ventral root in normal and experimental conditions

Development ◽  
1974 ◽  
Vol 32 (3) ◽  
pp. 819-833
Author(s):  
M. C. Prestige ◽  
Margaret A. Wilson
Keyword(s):  
Normal Development ◽  
Cell Number ◽  
Ventral Horn ◽  
Ventral Root ◽  
Limb Bud ◽  
Experimental Conditions ◽  
Collateral Sprouting ◽  
Cell Counts ◽  
Ventral Roots ◽  
Fibre Loss

1. The development of the ventral root (VR) in Xenopus has been studied by electron microscopy. Total fibre counts, and counts of classes of fibres were made from large photomontages of the whole of VR 9 at × 15000. 2. The total number of fibres in the root shows the same pattern of initial rise, peak, and subsequent decline that previous ventral horn (VH) cell counts had shown, The two curves overlay each other initially, but after the decline, there were apparently more cells than fibres. 3. Promyelin and myelin formation was seen at the time of the decline. There was no evidence that dying axons had started to myelinate. 4. In some animals the limb-bud was removed at the time of its first penetration by nerve fibres. The ventral roots developed normally for a week, but thereafter fibre loss was accentuated, advanced and more profound, so that after another week, no fibres were left. In these roots, no promyelin or myelin was formed. 5. In other animals, it was shown that there is no evidence for collateral sprouting in the ventral roots during normal development. 6. It is argued that the axons which die in normal development have already reached the limb-bud. 7. The correspondence between axon and cell number is discussed.

The fate of heritability in the postgenomic era

2012 ◽  
Vol 35 (5) ◽  
pp. 370-371
Author(s):  
Kevin MacDonald ◽  
Peter J. LaFreniere
Keyword(s):  
Maternal Effects ◽  
Environmental Effects ◽  
Normal Development ◽  
Behavior Genetic ◽  
Age Changes

AbstractThis commentary argues that age changes in heritability are incompatible with Charney's theory. The new genetics must be tempered by the findings that many epigenetic phenomena are random and are linked to pathology, thus making them peripheral to the design of complex adaptations. Behavior-genetic findings are compatible with strong maternal effects; G × E correlations likely underestimate environmental effects; and G × E interactions are unlikely to be an important aspect of normal development.

scholarly journals Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 13-28 ◽  
Author(s):  
S.L. Mansour ◽  
J.M. Goddard ◽  
M.R. Capecchi
Keyword(s):  
Inner Ear ◽  
Genetic Background ◽  
Mutant Allele ◽  
Primitive Streak ◽  
Otic Vesicle ◽  
Stochastic Variation ◽  
Targeted Disruption ◽  
Developmental Defects ◽  
Variable Expressivity ◽  
Reduced Penetrance

We derived mice that carry a targeted insertion of a neor gene in the int-2 (Fgf-3) proto-oncogene coding sequences. The mutation was found to be recessive and mice that were homozygous for the insertion did not often survive to adulthood. The mutant mice had defects in the development of the tail and inner ear that could be correlated with disruption of int-2 expression in the posterior primitive streak and hindbrain or otic vesicle. While the tail phenotype was 100% penetrant, we found that the inner ear phenotype had reduced penetrance and variable expressivity. The variable expressivity could not be attributed to variability in the genetic background of the mutant allele or to leaky expression from the mutant allele. Thus, we conclude that even in a uniform genetic background, stochastic variation in the expression of a developmental circuit can result in dramatic differences in phenotypic consequences.

scholarly journals A LAPS-Based Differential Sensor for Parallelized Metabolism Monitoring of Various Bacteria

Sensors ◽  
2019 ◽  
Vol 19 (21) ◽  
pp. 4692 ◽  
Author(s):  
Shahriar Dantism ◽  
Désirée Röhlen ◽  
Torsten Wagner ◽  
Patrick Wagner ◽  
Michael J. Schöning
Keyword(s):  
Fermentation Process ◽  
Metabolic Response ◽  
Ph Value ◽  
Cellular Metabolism ◽  
Cost Effective ◽  
Lactobacillus Brevis ◽  
Cell Number ◽  
Fermentation Processes ◽  
Number Variation ◽  
Set Up

Monitoring the cellular metabolism of bacteria in (bio)fermentation processes is crucial to control and steer them, and to prevent undesired disturbances linked to metabolically inactive microorganisms. In this context, cell-based biosensors can play an important role to improve the quality and increase the yield of such processes. This work describes the simultaneous analysis of the metabolic behavior of three different types of bacteria by means of a differential light-addressable potentiometric sensor (LAPS) set-up. The study includes Lactobacillus brevis, Corynebacterium glutamicum, and Escherichia coli, which are often applied in fermentation processes in bioreactors. Differential measurements were carried out to compensate undesirable influences such as sensor signal drift, and pH value variation during the measurements. Furthermore, calibration curves of the cellular metabolism were established as a function of the glucose concentration or cell number variation with all three model microorganisms. In this context, simultaneous (bio)sensing with the multi-organism LAPS-based set-up can open new possibilities for a cost-effective, rapid detection of the extracellular acidification of bacteria on a single sensor chip. It can be applied to evaluate the metabolic response of bacteria populations in a (bio)fermentation process, for instance, in the biogas fermentation process.

The response of the brachial ventral horn of Xenopus laevis to forelimb amputation during development

Development ◽  
1976 ◽  
Vol 36 (3) ◽  
pp. 453-468
Author(s):  
Joanne E. Fortune ◽  
Antonie W. Blackler
Keyword(s):  
Xenopus Laevis ◽  
Normal Development ◽  
Developmental Stages ◽  
Neuronal Degeneration ◽  
Neuronal Loss ◽  
Cell Loss ◽  
Cell Number ◽  
Ventral Horn ◽  
Cell Degeneration ◽  
Cell Numbers

The normal development of the brachial ventral horn of the frog Xenopus laevis and the response of the brachial ventral horn to complete forelimb extirpation at five developmental stages were assessed histologically. Differentiation of brachial ventral horn neurons occurred in pre-metamorphic tadpoles between stages 52/53 and 57. Mean cell number in the brachial ventral horn reached a peak of 2576 (S.E.M. = ±269, n = 2) per side of the spinal cord at stage 55 and decreased to 1070 (S.E.M. = ± 35, n =7) by the end of metamorphosis. Cell degeneration was presumed to be the mode of cell loss since it was most prevalent during the period of rapid decrease in cell numbers. The response of the ventral horn to forelimb removal varied with the stage of the animal at amputation. Following amputation at stage 52/53 or 54 the ipsilateral ventral horn neurons appeared less differentiated than those on the controlside and a rapid cell loss of about 80 % occurred on the operated side. These effects occurred more rapidly after ablation at stage 54 than at stage 52/53. Amputation at stage 58, 61, or 66 caused chromatolysis in the ventral horn, a period of relative cell excess on the operated side, and a delayed neuronal loss of 32–66%. It was concluded that excess cell degeneration accounted for cell loss and that suppression of normal neuronal degeneration caused the relative cell excess on the operated side. The data indicate that the brachial ventral horn was indifferent to the periphery before stage 54, was quickly affected by limb removal between stages 54 and 58, and by stage 58 had entered a phase in which a delay preceded cell death. No forelimb regeneration occurred.

scholarly journals Size matters: height, cell number and a person's risk of cancer

2018 ◽  
Vol 285 (1889) ◽  
pp. 20181743 ◽  
Author(s):  
Leonard Nunney
Keyword(s):  
Cancer Risk ◽  
Large Scale ◽  
Strong Relationship ◽  
Cell Number ◽  
Mammal Species ◽  
Division Rate ◽  
Multistage Model ◽  
Number Variation ◽  
Cancer Suppression ◽  
Risk Of Cancer

The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species. Consistent with this, the hazard ratio for overall cancer risk per 10 cm increase in human height (HR 10 ) is about 1.1, indicating a 10% increase in cancer risk per 10 cm; however, an alternative explanation invokes an indirect effect of height, with factors that increase cancer risk independently increasing adult height. The data from four large-scale surveillance projects on 23 cancer categories were tested against quantitative predictions of the cell-number hypothesis, predictions that were accurately supported. For overall cancer risk the HR 10 predicted versus observed was 1.13 versus 1.12 for women and 1.11 versus 1.09 for men, suggesting that cell number variation provides a null hypothesis for assessing height effects. Melanoma showed an unexpectedly strong relationship to height, indicating an additional effect, perhaps due to an increasing cell division rate mediated through increasing IGF-I with height. Similarly, only about one-third of the higher incidence of non-reproductive cancers in men versus women can be explained by cell number. The cancer risks of obesity are not correlated with effects of height, consistent with different primary causation. The direct effect of height on cancer risk suggests caution in identifying height-related SNPs as cancer causing.

scholarly journals Insights into CANDLE Syndrome

2020 ◽  
Vol 78 (1) ◽  
pp. 17-24
Author(s):  
Katarina Kieselová ◽  
Felicidade Santiago ◽  
Martinha Henrique
Keyword(s):  
Elevated Temperature ◽  
Genetic Background ◽  
Autoinflammatory Disease ◽  
Therapeutic Strategies ◽  
Neutrophilic Dermatosis

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a recently described chronic autoinflammatory disease, pathophysiologically related to intracellular proteasome/immunoproteasome dysfunction. This review chronicles the recognition of CANDLE syndrome, the developments in the understanding of the pathomechanism, genetic background, and the emerging therapeutic strategies of this condition.

The CDK inhibitor NtKIS1a is involved in plant development,endoreduplication and restores normal development of cyclin D3;1-overexpressing plants

2002 ◽  
Vol 115 (5) ◽  
pp. 973-982 ◽  
Author(s):  
Sophie Jasinski ◽  
Catherine Riou-Khamlichi ◽  
Odile Roche ◽  
Claudette Perennes ◽  
Catherine Bergounioux ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Plant Development ◽  
Normal Development ◽  
Control Cell ◽  
Cell Number ◽  
Cyclin D ◽  
Dependent Manner ◽  
Living Plant ◽  
Essentially Normal

Plant development requires stringent controls between cell proliferation and cell differentiation. Proliferation is positively regulated by cyclin dependent kinases (CDKs). Acting in opposition to CDKs are CDK inhibitors(CKIs). The first tobacco CKI (NtKIS1a) identified was shown to inhibit in vitro the kinase activity of CDK/cyclin complexes and to interact with CDK and D-cyclins. However, these features, which are common to other plant and animal CKIs already characterised, did not provide information about the function of NtKIS1a in plants. Thus, to gain insight into the role of NtKIS1a and especially its involvement in cell proliferation during plant development, we generated transgenic Arabidopsis thaliana plants that overexpress NtKIS1a. These plants showed reduced growth with smaller organs that contained larger cells. Moreover, these plants displayed modifications in plant morphology. These results demonstrated that plant organ size and shape,as well as organ cell number and cell size, might be controlled by modulation of the single NtKIS1a gene activity. Since in mammals, D-cyclins control cell cycle progression in a CDK-dependent manner but also play a CDK independent role by sequestering the CKIs p27Kip1 and p21Cip1, we tested the significance of cyclin D-CKI interaction within a living plant. With this aim, NtKIS1a and AtCycD3;1 were overexpressed simultaneously in plants by two different methods. Our results demonstrated that overexpression of the CKI NtKIS1a restores essentially normal development in plants overexpressing AtCycD3;1, providing the first evidence of cyclin D-CKI co-operation within the context of a living plant.

Aspect morphologique et composition chimique de Skeletonema costatum(Bacillariophyceae) croissant en milieu nutritif naturel à l'aide d'un système de culture à fibres dialysantes

1983 ◽  
Vol 29 (10) ◽  
pp. 1235-1240 ◽  
Author(s):  
Pierre Marsot ◽  
Marc Leclerc ◽  
Réal Fournier
Keyword(s):  
Normal Development ◽  
Skeletonema Costatum ◽  
Cell Number ◽  
Growth Stages ◽  
Biological Productivity ◽  
Composition Chimique ◽  
Average Cell ◽  
Growth Chambers ◽  
Culture Growth ◽  
Different Growth Stages

The growth of Skeletonema costatum, under natural nutriment conditions, was studied using a bulk culture fiber dialyzing apparatus. The diatom displayed normal development of chain length (average cell number per chain) which coincided with the culture growth stages; that is, the cell number per colony increased during the active division period and decreased thereafter with the beginning of the prestationary phase. This morphological behaviour showed that the alga cells were not affected by such physical shocks as collision or tension occurring during repeated cell transfers from growth chambers to the dialyzing apparatus or at the time of their passage through the fiber fascicles. Measured at different growth stages, the cell contents in carbon, nitrogen, and chlorophyll confirmed the above results and showed for S. costatum a biological productivity comparable with that obtained in smaller dialyzing containers (dialyzing bags). Through a comparison between the dialyzing culture and a static culture grown in an enriched medium, certain characteristics were determined.[Translated by the journal]

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