scholarly journals Pitx controls amphioxus asymmetric morphogenesis by promoting left-side development and repressing right-side formation

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chaofan Xing ◽  
Rongrong Pan ◽  
Guangwei Hu ◽  
Xian Liu ◽  
Yiquan Wang ◽  
...  
Keyword(s):  
Binding Sites ◽  
Essential Feature ◽  
Loss Of Function ◽  
Partial Loss ◽  
Developmental Mechanism ◽  
Right Isomerism ◽  
The Right ◽  
Insight Into ◽  
Made In

Abstract Background Left-right (LR) asymmetry is an essential feature of bilateral animals. Studies in vertebrates show that LR asymmetry formation comprises three major steps: symmetry breaking, asymmetric gene expression, and LR morphogenesis. Although much progress has been made in the first two events, mechanisms underlying asymmetric morphogenesis remain largely unknown due to the complex developmental processes deployed by vertebrate organs. Results We here addressed this question by studying Pitx gene function in the basal chordate amphioxus whose asymmetric organogenesis, unlike that in vertebrates, occurs essentially in situ and does not rely on cell migration. Pitx null mutation in amphioxus causes loss of all left-sided organs and incomplete ectopic formation of all right-sided organs on the left side, whereas Pitx partial loss-of-function leads to milder phenotypes with only some LR organs lost or ectopically formed. At the N1 to N3 stages, Pitx expression is gradually expanded from the dorsal anterior domain to surrounding regions. This leads to activation of genes like Lhx3 and/or Prop1 and Pit, which are essential for left-side organs, and downregulation of genes like Hex and/or Nkx2.1 and FoxE4, which are required for right-side organs to form ectopically on the left side. In Pitx mutants, the left-side expressed genes are not activated, while the right-side genes fail to decrease expression on the left side. In contrast, in embryos overexpressing Pitx genes, the left-side genes are induced ectopically on the right side, and the right-side genes are inhibited. Several Pitx binding sites are identified in the upstream sequences of the left-side and right-side genes which are essential for activation of the former and repression of the latter by Pitx. Conclusions Our results demonstrate that (1) Pitx is a major (although not the only) determinant of asymmetric morphogenesis in amphioxus, (2) the development of different LR organs have distinct requirements for Pitx activity, and (3) Pitx controls amphioxus LR morphogenesis probably through inducing left-side organs and inhibiting right-side organs directly. These findings show much more dependence of LR organogenesis on Pitx in amphioxus than in vertebrates. They also provide insight into the molecular developmental mechanism of some vertebrate LR organs like the lungs and atria, since they show a right-isomerism phenotype in Pitx2 knockout mice like right-sided organs in Pitx mutant amphioxus. Our results also explain why some organs like the adenohypophysis are asymmetrically located in amphioxus but symmetrically positioned in vertebrates.

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve

1998 ◽  
Vol 274 (1) ◽  
pp. H358-H365 ◽  
Author(s):  
Takayuki Sato ◽  
Toru Kawada ◽  
Toshiaki Shishido ◽  
Hiroshi Miyano ◽  
Masashi Inagaki ◽  
...  
Keyword(s):  
Transfer Function ◽  
White Noise ◽  
Innominate Artery ◽  
Operating Pressure ◽  
Frequency Range ◽  
Aortic Depressor Nerve ◽  
The Right ◽  
Common Carotid Arteries ◽  
Made In

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01–5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was >0.8 in the frequency range of 0.01–4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

scholarly journals Update on novel targets and potential treatment avenues in pulmonary hypertension

2016 ◽  
Vol 311 (5) ◽  
pp. L811-L831 ◽  
Author(s):  
John C. Huetsch ◽  
Karthik Suresh ◽  
Meghan Bernier ◽  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
Cellular Processes ◽  
Perivascular Inflammation ◽  
Altered Metabolism ◽  
The Right ◽  
Cellular Pathology ◽  
Reactive Oxygen Species Signaling ◽  
Insight Into ◽  
Made In

Pulmonary hypertension (PH) is a condition marked by a combination of constriction and remodeling within the pulmonary vasculature. It remains a disease without a cure, as current treatments were developed with a focus on vasodilatory properties but do not reverse the remodeling component. Numerous recent advances have been made in the understanding of cellular processes that drive pathologic remodeling in each layer of the vessel wall as well as the accompanying maladaptive changes in the right ventricle. In particular, the past few years have yielded much improved insight into the pathways that contribute to altered metabolism, mitochondrial function, and reactive oxygen species signaling and how these pathways promote the proproliferative, promigratory, and antiapoptotic phenotype of the vasculature during PH. Additionally, there have been significant advances in numerous other pathways linked to PH pathogenesis, such as sex hormones and perivascular inflammation. Novel insights into cellular pathology have suggested new avenues for the development of both biomarkers and therapies that will hopefully bring us closer to the elusive goal: a therapy leading to reversal of disease.

scholarly journals Expanding or postponing? Patterns of negotiation in multi-party interactions in social work

2017 ◽  
Vol 11 (5) ◽  
pp. 483-497 ◽  
Author(s):  
Tanja Dall ◽  
Dorte Caswell
Keyword(s):  
Social Work ◽  
Analytical Approach ◽  
Work Setting ◽  
Team Members ◽  
Team Meetings ◽  
Negotiated Order ◽  
Insight Into ◽  
Institutional Order ◽  
Made In

In this article, we examine patterns of negotiation in multi-party decision making in social work. We draw on Strauss’ theory of negotiated order and a discourse analytical approach, seeking to gain insight into the complex accomplishment of making a decision in an inter-professional and multi-party setting. Working with data from 97 team meetings in a social work setting, we identify two patterns of negotiation in talk: expanding and postponing. ‘Expanding’ covers a group of interactional actions involving turn-taking and closure, while ‘postponing’ includes a group of actions whereby assessments or topics are avoided or made irrelevant. Both are examples of the complex ways in which team members negotiate both the institutional order and the decision to be made in the specific case in situ.

scholarly journals Developmental regulation of expression of the lactate dehydrogenase (LDH) multigene family during mouse spermatogenesis

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 483-493 ◽  
Author(s):  
K. Thomas ◽  
J. Del Mazo ◽  
P. Eversole ◽  
A. Bellve ◽  
Y. Hiraoka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lactate Dehydrogenase ◽  
Developmental Regulation ◽  
Regulation Of Gene Expression ◽  
Regulation Of Expression ◽  
Sequence Of Events ◽  
Pachytene Spermatocytes ◽  
Insight Into ◽  
Made In

Expression of the Lactate Dehydrogenase (LDH) genes during various stages of spermatogenesis was studied by using a combination of Northern blot analyses and in situ hybridization techniques. These studies have indicated that developmentally programmed expression of all three functional LDH genes occurs during differentiation of germ cells. The LDH/C (ldh-3) gene was expressed exclusively during meiosis and spermiogenesis, beginning in leptotene/zygotene spermatocytes and continuing through to the elongated spermatids. LDH/C (ldh-3) gene expression was accompanied by transient expression of the LDH/A (ldh-1) gene in pachytene spermatocytes and round spermatids. The LDH/B (ldh-2) gene was expressed mainly in Sertoli and spermatogonial cells. By using somatic cell hybrids, the LDH/C (ldh-3) gene has been mapped to mouse chromosome 7, establishing that it is syntenic with the LDH/A (ldh-1) gene locus. Experimental observations made in this study provide new insight into the order and sequence of events involved in the regulation of gene expression of the LDH gene family during spermatogenesis.

Abstract 283: Nppa Marks A Subset Of Embryonic Cardiomyocytes Predestined To Form Trabeculae In Zebrafish

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Rima Arnaout ◽  
Didier Y Stainier ◽  
Shaun R Coughlin
Keyword(s):  
Zebrafish Embryo ◽  
Transgenic Zebrafish ◽  
Loss Of Function ◽  
Atrial Contraction ◽  
Embryonic Cardiomyocytes ◽  
External Development ◽  
Insight Into ◽  
Spinning Disc ◽  
Atrial Myosin

The development and maintenance of cardiac trabeculae is required for proper ventricular function. Aberrant trabeculation can cause heart failure, arrhythmia, and death. Yet the mechanisms controlling initiation of trabeculation are incompletely understood, partly due to a lack of markers for trabeculation during early embryogenesis. We hypothesized that natriuretic peptide A (nppa) marks trabeculae before cardiomyocytes leave the single-celled ventricular layer. While nppa has been studied in mammals, the external development of the translucent zebrafish embryo offers new insight into the earliest stages of trabeculation. We have found by in situ hybridization, and by creating a fluorescent transgenic zebrafish line, that nppa exclusively marks zebrafish cardiac trabeculae from their onset through adulthood. Live spinning disc confocal video microscopy shows that nppa:GFP-positive cells move into the trabecular layer starting at 60 hours post fertilization (hpf). GFP-positive trabeculae are seen by 5 days post fertilization (dpf) in normal larvae. However, in cardiac troponin T2a mutants and in erbB2 mutants _ both known not to trabeculate _ nppa is still expressed, but the nppa:GFP positive cells fail to form trabecular projections. In embryos injected with a morpholino against atrial myosin heavy chain 6, where weakened atrial contraction leads to weaker blood flow without affecting the ventricle directly, GFP-positive cells form trabeculae similar to uninjected controls. Using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs), we created nppa mutants causing frameshift deletions. Mutants have poorly contractile hearts at 3 dpf and have been crossed into transgenic reporter lines in order to specifically assess trabeculation. Together, these data suggest that nppa marks a subset of embryonic cardiomyocytes destined to form trabeculae, and that nppa loss of function causes cardiac defects.

scholarly journals The CD33 short isoform is a gain-of-function variant that enhances Aβ1–42 phagocytosis in microglia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Abhishek Bhattacherjee ◽  
Jaesoo Jung ◽  
Sameera Zia ◽  
Madelene Ho ◽  
Ghazaleh Eskandari-Sedighi ◽  
...  
Keyword(s):  
Cell Lineage ◽  
Strong Support ◽  
U937 Cells ◽  
Loss Of Function ◽  
Primary Microglia ◽  
Gain Of Function ◽  
Intracellular Location ◽  
Insight Into

Abstract Background CD33 is genetically linked to Alzheimer’s disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant. Methods We have developed two models to test the role of hCD33m. The first is a new strain of transgenic mice expressing hCD33m in the microglial cell lineage. The second is U937 cells where the CD33 gene was disrupted by CRISPR/Cas9 and complemented with different variants of hCD33. Primary microglia and U937 cells were tested in phagocytosis assays and single cell RNA sequencing (scRNAseq) was carried out on the primary microglia. Furthermore, a new monoclonal antibody was developed to detect hCD33m more efficiently. Results In both primary microglia and U937 cells, we find that hCD33m enhances phagocytosis. This contrasts with the human CD33 long isoform (hCD33M) that represses phagocytosis, as previously demonstrated. As revealed by scRNAseq, hCD33m+ microglia are enriched in a cluster of cells defined by an upregulated expression and gene regulatory network of immediate early genes, which was further validated within microglia in situ. Using a new hCD33m-specific antibody enabled hCD33m expression to be examined, demonstrating a preference for an intracellular location. Moreover, this newly discovered gain-of-function role for hCD33m is dependent on its cytoplasmic signaling motifs, dominant over hCD33M, and not due to loss of glycan ligand binding. Conclusions These results provide strong support that hCD33m represents a gain-of-function isoform and offers insight into what it may take to therapeutically capture the AD-protective CD33 allele.

scholarly journals ANOMALOUS PREVERTEBRAL COURSE OF THE LEFT VERTEBRAL ARTERY. Recorrido prevertebral anómalo de la arteria vertebral izquierda

2016 ◽  
Vol 6 (3) ◽  
pp. 176-179
Author(s):  
Prakash B Billakanti
Keyword(s):  
Vertebral Artery ◽  
Present Report ◽  
Left Vertebral Artery ◽  
Thoracic Region ◽  
Developmental Mechanism ◽  
Arch Of The Aorta ◽  
The Right ◽  
The Brain ◽  
Variant Anatomy ◽  
Insight Into

La arteria vertebral es una de las arterias que irriga el cerebro. El conocimiento de la anatomía normal y las variantes de la arteria vertebral adquiere importancia en la práctica clínica y la radiología vascular. El origen anómalo de la arteria vertebral del arco de la aorta o cualquiera de las arterias del cuello ha sido reportado por muchos autores. En este informe se presenta una variación del curso prevertebral de la arteria vertebral izquierda. La arteria vertebral tenía su origen habitual en la arteria subclavia con un largo curso prevertebral y entraba en el foramen transversarium de la vértebra CII. El origen y recorrido de la arteria vertebral en el lado derecho fue normal. Clínicamente es importante conocer el origen y curso del segmento prevertebral de la arteria vertebral y las posibles variaciones. El presente informe debería ser de interés para el médico vascular con respecto a las variaciones en el cuello y región torácica, y puede dar idea para dilucidar el mecanismo de desarrollo de la angiogénesis. Vertebral artery is one of the arteries supplying the brain. Knowledge of the normal and variant anatomy of the vertebral artery assumes importance in clinical practice and vascular radiology. Anomalous origins of the vertebral artery from the arch of the aorta or any one of the arteries of the neck have been reported by several authors. In this report a variation of the prevertebral course of the left vertebral artery is being presented. The Vertebral artery had usual origin from the subclavian artery and had a longer prevertebral course to enter the foramen transversarium of the CII vertebra. The origin and course of the vertebral artery on the right side was normal. It is clinically important to know the origin and course of the prevertebral segment of the vertebral artery and possible variations. The present report should be of interest for clinicians with regard to vascular variations in the neck and thoracic region, and may give insight into elucidating the developmental mechanism of angiogenesis.

scholarly journals The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4654-4663 ◽  
Author(s):  
Julio D. Amigo ◽  
Gabriele E. Ackermann ◽  
John J. Cope ◽  
Ming Yu ◽  
Jeffrey D. Cooney ◽  
...  
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Loss Of Function ◽  
Gata Factors ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells ◽  
Regulatory Loop

Abstract The nuclear protein FOG-1 binds transcription factor GATA-1 to facilitate erythroid and megakaryocytic maturation. However, little is known about the function of FOG-1 during myeloid and lymphoid development or how FOG-1 expression is regulated in any tissue. We used in situ hybridization, gain- and loss-of-function studies in zebrafish to address these problems. Zebrafish FOG-1 is expressed in early hematopoietic cells, as well as heart, viscera, and paraspinal neurons, suggesting that it has multifaceted functions in organogenesis. We found that FOG-1 is dispensable for endoderm specification but is required for endoderm patterning affecting the expression of late-stage T-cell markers, independent of GATA-1. The suppression of FOG-1, in the presence of normal GATA-1 levels, induces severe anemia and thrombocytopenia and expands myeloid-progenitor cells, indicating that FOG-1 is required during erythroid/myeloid commitment. To functionally interrogate whether GATA-1 regulates FOG-1 in vivo, we used bioinformatics combined with transgenic assays. Thus, we identified 2 cis-regulatory elements that control the tissue-specific gene expression of FOG-1. One of these enhancers contains functional GATA-binding sites, indicating the potential for a regulatory loop in which GATA factors control the expression of their partner protein FOG-1.

Experimental study of the formation of the bulboventricular loop in the chick

Development ◽  
1972 ◽  
Vol 27 (3) ◽  
pp. 623-637
Author(s):  
Alfredo Castro-Quezada ◽  
Bernardo Nadal-Ginard ◽  
María V. de la Cruz
Keyword(s):  
Electron Microscope ◽  
Time Lapse ◽  
Mirror Image ◽  
Heart Tube ◽  
Removal Experiments ◽  
Atrioventricular Groove ◽  
The Right ◽  
Time Lapse Photography ◽  
Made In

The formation of the normal bulboventricular loop (convex to the right) and the inverted loop (convex to the left) produced by the Lepori technique in chick embryos was studied. The development of the loops was recorded by means of diagrams, photographs and microscopic time-lapse photography. Electron-microscope studies were also made. The normal loop was studied by means of labelling and removal experiments on the heart tube. The results demonstrated that the fusion of both cardiac primordia is made in stage 9 — in the mid-line of the embryo and that the first asymmetry of the heart tube appears in stage 10. The truncus region developed in situ directed towards the right after the fusion of both cardiac primordia, and in this region the electron-microscope study demonstrated a gradient of caudo-cephalic differentiation. In stage 10 the left caudal groove is the prospective interventricular groove, but the right caudal groove is not the right atrioventricular groove as had been stated by others. The asymmetric incorporation of both primordia begins in stage 11 —, when the curvature of the loop is already developing. In the removal experiments it was evident that the different portions of the cardiac tube in situ are orientated in space independently of the whole of the loop. The formation of the experimentally inverted loop is a mirror-image of the normal loop and appears to be originated through mechanic traction of the cardiac tube by the left splachnopleure and not by a faster displacement of the right cardiac primordia.

Electron Probe Analysis of Muscle

1982 ◽  
Vol 40 ◽  
pp. 398-401
Author(s):  
A. V. Somlyo ◽  
H. Shuman ◽  
A. P. Somlyo
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Resting State ◽  
Binding Sites ◽  
Electron Probe ◽  
Frog Skeletal Muscle ◽  
Electron Probe Analysis ◽  
Probe Analysis

Electron probe analysis of frozen dried cryosections of frog skeletal muscle, rabbit vascular smooth muscle and of isolated, hyperpermeab1 e rabbit cardiac myocytes has been used to determine the composition of the cytoplasm and organelles in the resting state as well as during contraction. The concentration of elements within the organelles reflects the permeabilities of the organelle membranes to the cytoplasmic ions as well as binding sites. The measurements of [Ca] in the sarcoplasmic reticulum (SR) and mitochondria at rest and during contraction, have direct bearing on their role as release and/or storage sites for Ca in situ.

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