Determination of the embryonic axes of Drosophila*

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 1-10 ◽  
Author(s):  
Christiane Nüsslein-Volhard

The principles of embryonic pattern formation have been studied extensively in many systems using classical experimental approaches. In Drosophila, a powerful combination of genetics and transplantation experiments, as well as molecular biology, have helped to elucidate the mechanisms that operate during oogenesis and early embryogenesis to establish a set of positional cues required for axis determination in the early embryo. In systematic searches for maternal effect mutations a small number of about 30 genes have been identified that specifically affect the process of determination of the embryonic axes. These ‘coordinate’ genes define four systems that determine the anteroposterior (AP) axis (three systems) and the dorsoventral (DV) axis (one system) independently. In the anteroposterior axis, the anterior system determines the segmented region of head and thorax, the posterior system determines the segmented abdominal region, and the terminal system is responsible for the formation of the nonsegmented termini at the anterior and posterior egg tips, the acron and telson. In contrast, pattern along the dorsoventral axis is determined by one system only. Although all four systems use different biochemical mechanisms, they share several properties. (1) The product of one gene in each system is localized in a specific region of the freshly laid egg and functions as a spatial signal. (2) In each system, this spatial information finally results in the asymmetrical distribution of one gene product that functions as a transcription factor. (3) This transcription factor is distributed in a concentration gradient that defines the spatial limits of expression of one or more zygotic target genes. The combined action of these three anteroposterior systems as well as the dorsoventral system defines the expression of zygotic target genes in at least seven distinct regions along the anteroposterior and at least three in the dorsoventral axis. These longitudinal and transverse domains provide a coarse spatial prepattern which is then further refined by the action and interaction of zygotic pattern genes.

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 191-200 ◽  
Author(s):  
A. Sapir ◽  
R. Schweitzer ◽  
B.Z. Shilo

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.


2021 ◽  
Author(s):  
Lindsay A. Phillips ◽  
Markle L. Atienza ◽  
Jae-Ryeon Ryu ◽  
Pia C. Svendsen ◽  
Lynn K. Kelemen ◽  
...  

AbstractVentral leg patterning in Drosophila is controlled by the expression of the redundant T-box Transcription factors midline (mid) and H15. Here we show that mid represses the Dpp-activated gene Daughters against decapentaplegic (Dad) through a consensus TBE site in the minimal enhancer, Dad13. Mutating the Dad13 DNA sequence results in an increased and broadening of Dad expression. We further demonstrate that the engrailed-homology-1 domain of Mid is critical for regulating the levels of phospho-Mad, a transducer of Dpp-signaling. However, we find that mid does not affect all Dpp-target genes as we demonstrate that brinker (brk) expression is unresponsive to mid. This study further illuminates the interplay between mechanisms involved in determination of cellular fate and the varied roles of mid.Summary statementVentral patterning is controlled in part by the T-box Transcription factor midline blocking Dpp signaling and Dpp-activated genes, though midline does not affect the Dpp-repressed gene brk.


1971 ◽  
Vol 26 (02) ◽  
pp. 275-288 ◽  
Author(s):  
S Chattopadhyay ◽  
D. D Johnson ◽  
G. J Millar ◽  
L. B Jaques

SummaryRats were subjected to the following procedures: No treatment, Stressor (10% NaCl i.p.), Warfarin for 7 days, Stressor followed by Warfarin; and groups were sacrificed at intervals for assessment of spontaneous hemorrhage and of adrenal ascorbic acid concentration. There was no hemorrhage in the no treatment and stressor groups; some hemorrhage in the warfarin group; profound hemorrhage with Warfarin + Stressor. The adrenal ascorbic acid concentration was found to be lower, 8 h and again 5 days after stress, and remained lower in the warfarin + stress animals. Warfarin had no effect on adrenal ascorbic acid level.In another series of experiments in which the stress consisted of an electric current to the cage floor for 6 sec over 15 min, rats were sacrificed daily for determination of serum corticosterone concentration and occurrence of spontaneous hemorrhage. There was a statistically significant increase of serum corticosterone concentration with stress, warfarin and combined warfarin and stress treatments (P< 0.001 for all three variables). There was a significant correlation (r = 0.96 and 0.89, P< 0.01) for serum corticosterone concentration with hemorrhage score and incidence of hemorrhage in stressed rats receiving warfarin, but not in those receiving only warfarin. The results indicate an activation, rather than an exhaustion, of the pituitary-adrenal axis during the combined action of anticoagulant and stress, which results in the development of spontaneous hemorrhage.


2021 ◽  
pp. 1-9
Author(s):  
Javier Carrillo-Reche ◽  
Adrian C. Newton ◽  
Richard S. Quilliam

Abstract A low-cost technique named ‘on-farm’ seed priming is increasingly being recognized as an effective approach to maximize crop establishment. It consists of anaerobically soaking seeds in water before sowing resulting in rapid and uniform germination, and enhanced seedling vigour. The extent of these benefits depends on the soaking time. The current determination of optimal soaking time by germination assays and mini-plot trials is resource-intensive, as it is species/genotype-specific. This study aimed to determine the potential of the seed respiration rate (an indicator of metabolic activity) and seed morphological changes during barley priming as predictors of the priming benefits and, thus, facilitate the determination of optimal soaking times. A series of germination tests revealed that the germination rate is mostly attributable to the rapid hydration of embryo tissues, as the highest gains in the germination rate occurred before the resumption of respiration. Germination uniformity, however, was not significantly improved until seeds were primed for at least 8 h, that is, after a first respiration burst was initiated. The maximum seedling vigour was attained when the priming was stopped just before the beginning of the differentiation of embryonic axes (20 h) after which vigour began to decrease (‘over-priming’). The onset of embryonic axis elongation was preceded by a second respiration burst, which can be used as a marker for priming optimization. Thus, monitoring of seed respiration provides a rapid and inexpensive alternative to the current practice. The method could be carried out by agricultural institutions to provide recommended optimal soaking times for the common barley varieties within a specific region.


2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.


2021 ◽  
Vol 22 (14) ◽  
pp. 7627
Author(s):  
Tingting Shi ◽  
Asahiro Morishita ◽  
Hideki Kobara ◽  
Tsutomu Masaki

Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA.


2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Vishwanie S. Budhram-Mahadeo ◽  
Matthew R. Solomons ◽  
Eeshan A. O. Mahadeo-Heads

AbstractMetabolic and cardiovascular diseases are highly prevalent and chronic conditions that are closely linked by complex molecular and pathological changes. Such adverse effects often arise from changes in the expression of genes that control essential cellular functions, but the factors that drive such effects are not fully understood. Since tissue-specific transcription factors control the expression of multiple genes, which affect cell fate under different conditions, then identifying such regulators can provide valuable insight into the molecular basis of such diseases. This review explores emerging evidence that supports novel and important roles for the POU4F2/Brn-3b transcription factor (TF) in controlling cellular genes that regulate cardiometabolic function. Brn-3b is expressed in insulin-responsive metabolic tissues (e.g. skeletal muscle and adipose tissue) and is important for normal function because constitutive Brn-3b-knockout (KO) mice develop profound metabolic dysfunction (hyperglycaemia; insulin resistance). Brn-3b is highly expressed in the developing hearts, with lower levels in adult hearts. However, Brn-3b is re-expressed in adult cardiomyocytes following haemodynamic stress or injury and is necessary for adaptive cardiac responses, particularly in male hearts, because male Brn-3b KO mice develop adverse remodelling and reduced cardiac function. As a TF, Brn-3b regulates the expression of multiple target genes, including GLUT4, GSK3β, sonic hedgehog (SHH), cyclin D1 and CDK4, which have known functions in controlling metabolic processes but also participate in cardiac responses to stress or injury. Therefore, loss of Brn-3b and the resultant alterations in the expression of such genes could potentially provide the link between metabolic dysfunctions with adverse cardiovascular responses, which is seen in Brn-3b KO mutants. Since the loss of Brn-3b is associated with obesity, type II diabetes (T2DM) and altered cardiac responses to stress, this regulator may provide a new and important link for understanding how pathological changes arise in such endemic diseases.


2020 ◽  
Author(s):  
Seungwoo Cha ◽  
Chang Pyo Hong ◽  
Hyun Ah Kang ◽  
Ji-Sook Hahn

Abstract Gcr1, an important transcription factor for glycolytic genes in Saccharomyces cerevisiae, was recently revealed to have two isoforms, Gcr1U and Gcr1S, produced from un-spliced and spliced transcripts, respectively. In this study, by generating strains expressing only Gcr1U or Gcr1S using the CRISPR/Cas9 system, we elucidate differential activation mechanisms of these two isoforms. The Gcr1U monomer forms an active complex with its coactivator Gcr2 homodimer, whereas Gcr1S acts as a homodimer without Gcr2. The USS domain, 55 residues at the N-terminus existing only in Gcr1U, inhibits dimerization of Gcr1U and even acts in trans to inhibit Gcr1S dimerization. The Gcr1S monomer inhibits the metabolic switch from fermentation to respiration by directly binding to the ALD4 promoter, which can be restored by overexpression of the ALD4 gene, encoding a mitochondrial aldehyde dehydrogenase required for ethanol utilization. Gcr1U and Gcr1S regulate almost the same target genes, but show unique activities depending on growth phase, suggesting that these isoforms play differential roles through separate activation mechanisms depending on environmental conditions.


2004 ◽  
Vol 101 (28) ◽  
pp. 10458-10463 ◽  
Author(s):  
A. W. Bruce ◽  
I. J. Donaldson ◽  
I. C. Wood ◽  
S. A. Yerbury ◽  
M. I. Sadowski ◽  
...  

Genomics ◽  
2017 ◽  
Vol 109 (2) ◽  
pp. 75-82 ◽  
Author(s):  
Mirana Ramialison ◽  
Ashley J. Waardenberg ◽  
Nicole Schonrock ◽  
Tram Doan ◽  
Danielle de Jong ◽  
...  

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