Mutations affecting the formation of the notochord in the zebrafish, Danio rerio

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 103-115 ◽  
Author(s):  
J. Odenthal ◽  
P. Haffter ◽  
E. Vogelsang ◽  
M. Brand ◽  
F.J. van Eeden ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Large Scale ◽  
Floor Plate ◽  
Precursor Cells ◽  
Wild Type ◽  
Plate Formation ◽  
Notochord Cells ◽  
The Right ◽  
Adaxial Cells

In a large scale screen for mutants with defects in the embryonic development of the zebrafish we identified mutations in four genes, floating head (flh), momo (mom), no tail (ntl), and doc, that are required for early notochord formation. Mutations in flh and ntl have been described previously, while mom and doc are newly identified genes. Mutant mom embryos lack a notochord in the trunk, and trunk somites from the right and left side of the embryo fuse underneath the neural tube. In this respect mom appears similar to flh. In contrast, notochord precursor cells are present in both ntl and doc embryos. In order to gain a greater understanding of the phenotypes, we have analysed the expression of several axial mesoderm markers in mutant embryos of all four genes. In flh and mom, Ntl expression is normal in the germ ring and tailbud, while the expression of Ntl and other notochord markers in the axial mesodermal region is disrupted. Ntl expression is normal in doc embryos until early somitic stages, when there is a reduction in expression which is first seen in anterior regions of the embryo. This suggests a function for doc in the maintenance of ntl expression. Other notochord markers such as twist, sonic hedgehog and axial are not expressed in the axial mesoderm of ntl embryos, their expression parallels the expression of ntl in the axial mesoderm of mutant doc, flh and mom embryos, indicating that ntl is required for the expression of these markers. The role of doc in the expression of the notochord markers appears indirect via ntl. Floor plate formation is disrupted in most regions in flh and mom mutant embryos but is present in mutant ntl and doc embryos. In mutant embryos with strong ntl alleles the band of cells expressing floor plate markers is broadened. A similar broadening is also observed in the axial mesoderm underlying the floor plate of ntl embryos, suggesting a direct involvement of the notochord precursor cells in floor plate induction. Mutations in all of these four genes result in embryos lacking a horizontal myoseptum and muscle pioneer cells, both of which are thought to be induced by the notochord. These somite defects can be traced back to an impairment of the specification of the adaxial cells during early stages of development. Transplantation of wild-type cells into mutant doc embryos reveals that wild-type notochord cells are sufficient to induce horizontal myoseptum formation in the flanking mutant tissue. Thus doc, like flh and ntl, acts cell autonomously in the notochord. In addition to the four mutants with defects in early notochord formation, we have isolated 84 mutants, defining at least 15 genes, with defects in later stages of notochord development. These are listed in an appendix to this study.

scholarly journals Natural Zeitgebers Under Temperate Conditions Cannot Compensate for the Loss of a Functional Circadian Clock in Timing of a Vital Behavior in Drosophila

2021 ◽  
pp. 074873042199811
Author(s):  
Franziska Ruf ◽  
Oliver Mitesser ◽  
Simon Tii Mungwa ◽  
Melanie Horn ◽  
Dirk Rieger ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Time Window ◽  
Fruit Fly ◽  
Diel Activity ◽  
Wild Type ◽  
Statistical Measures ◽  
Clock Mutant ◽  
Full Complement ◽  
The Right

The adaptive significance of adjusting behavioral activities to the right time of the day seems obvious. Laboratory studies implicated an important role of circadian clocks in behavioral timing and rhythmicity. Yet, recent studies on clock-mutant animals questioned this importance under more naturalistic settings, as various clock mutants showed nearly normal diel activity rhythms under seminatural zeitgeber conditions. We here report evidence that proper timing of eclosion, a vital behavior of the fruit fly Drosophila melanogaster, requires a functional molecular clock under quasi-natural conditions. In contrast to wild-type flies, period01 mutants with a defective molecular clock showed impaired rhythmicity and gating in a temperate environment even in the presence of a full complement of abiotic zeitgebers. Although period01 mutants still eclosed during a certain time window during the day, this time window was much broader and loosely defined, and rhythmicity was lower or lost as classified by various statistical measures. Moreover, peak eclosion time became more susceptible to variable day-to-day changes of light. In contrast, flies with impaired peptidergic interclock signaling ( Pdf01 and han5304 PDF receptor mutants) eclosed mostly rhythmically with normal gate sizes, similar to wild-type controls. Our results suggest that the presence of natural zeitgebers is not sufficient, and a functional molecular clock is required to induce stable temporal eclosion patterns in flies under temperate conditions with considerable day-to-day variation in light intensity and temperature. Temperate zeitgebers are, however, sufficient to functionally rescue a loss of PDF-mediated clock-internal and -output signaling

The zebrafish T-box genesno tailandspadetailare required for development of trunk and tail mesoderm and medial floor plate

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3311-3323 ◽  
Author(s):  
Sharon L. Amacher ◽  
Bruce W. Draper ◽  
Brian R. Summers ◽  
Charles B. Kimmel
Keyword(s):  
Embryonic Development ◽  
Neural Tube ◽  
Transcriptional Regulators ◽  
Floor Plate ◽  
Wild Type ◽  
T Box ◽  
No Tail ◽  
Ventral Neural Tube ◽  
Plate Formation ◽  
In Cells

T-box genes encode transcriptional regulators that control many aspects of embryonic development. Here, we demonstrate that the mesodermally expressed zebrafish spadetail (spt)/VegT and no tail (ntl)/Brachyury T-box genes are semi-redundantly and cell-autonomously required for formation of all trunk and tail mesoderm. Despite the lack of posterior mesoderm in spt–;ntl– embryos, dorsal-ventral neural tube patterning is relatively normal, with the notable exception that posterior medial floor plate is completely absent. This contrasts sharply with observations in single mutants, as mutations singly in ntl or spt enhance posterior medial floor plate development. We find that ntl function is required to repress medial floor plate and promote notochord fate in cells of the wild-type notochord domain and that spt and ntl together are required non cell-autonomously for medial floor plate formation, suggesting that an inducing signal present in wild-type mesoderm is lacking in spt–;ntl– embryos.

Identifying neuroanatomical signatures in insomnia and migraine comorbidity

SLEEP ◽  
2020 ◽  
Author(s):  
Kun-Hsien Chou ◽  
Pei-Lin Lee ◽  
Chih-Sung Liang ◽  
Jiunn-Tay Lee ◽  
Hung-Wen Kao ◽  
...  
Keyword(s):  
Large Scale ◽  
Gray Matter Volume ◽  
Brain Structures ◽  
Brain Network ◽  
Structural Covariance ◽  
Matter Volume ◽  
The Right ◽  
Global Brain ◽  
The Brain

Abstract Study Objectives While insomnia and migraine are often comorbid, the shared and distinct neuroanatomical substrates underlying these disorders and the brain structures associated with the comorbidity are unknown. We aimed to identify patterns of neuroanatomical substrate alterations associated with migraine and insomnia comorbidity. Methods High-resolution T1-weighted images were acquired from subjects with insomnia, migraine, and comorbid migraine and insomnia, respectively, and healthy controls (HC). Direct group comparisons with HC followed by conjunction analyses identified shared regional gray matter volume (GMV) alterations between the disorders. To further examine large-scale anatomical network changes, a seed-based structural covariance network (SCN) analysis was applied. Conjunction analyses also identified common SCN alterations in two disease groups, and we further evaluated these shared regional and global neuroanatomical signatures in the comorbid group. Results Compared with controls, patients with migraine and insomnia showed GMV changes in the cerebellum and the lingual, precentral, and postcentral gyri (PCG). The bilateral PCG were common GMV alteration sites in both groups, with decreased structural covariance integrity observed in the cerebellum. In patients with comorbid migraine and insomnia, shared regional GMV and global SCN changes were consistently observed. The GMV of the right PCG also correlated with sleep quality in these patients. Conclusion These findings highlight the specific role of the PCG in the shared pathophysiology of insomnia and migraine from a regional and global brain network perspective. These multilevel neuroanatomical changes could be used as potential image markers to decipher the comorbidity of the two disorders.

scholarly journals The Potential Role of Genomic Medicine in the Therapeutic Management of Rheumatoid Arthritis

2019 ◽  
Vol 8 (6) ◽  
pp. 826 ◽  
Author(s):  
Marialbert Acosta-Herrera ◽  
David González-Serna ◽  
Javier Martín
Keyword(s):  
Rheumatoid Arthritis ◽  
Large Scale ◽  
Rare Variants ◽  
Drug Repositioning ◽  
Genomic Medicine ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Genomic Studies ◽  
The Right

During the last decade, important advances have occurred regarding understanding of the pathogenesis and treatment of rheumatoid arthritis (RA). Nevertheless, response to treatment is not universal, and choosing among different therapies is currently based on a trial and error approach. The specific patient’s genetic background influences the response to therapy for many drugs: In this sense, genomic studies on RA have produced promising insights that could help us find an effective therapy for each patient. On the other hand, despite the great knowledge generated regarding the genetics of RA, most of the investigations performed to date have focused on identifying common variants associated with RA, which cannot explain the complete heritability of the disease. In this regard, rare variants could also contribute to this missing heritability as well as act as biomarkers that help in choosing the right therapy. In the present article, different aspects of genetics in the pathogenesis and treatment of RA are reviewed, from large-scale genomic studies to specific rare variant analyses. We also discuss the shared genetic architecture existing among autoimmune diseases and its implications for RA therapy, such as drug repositioning.

scholarly journals Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea

2015 ◽  
Vol 112 (12) ◽  
pp. 3746-3751 ◽  
Author(s):  
Eun Jin Son ◽  
Ji-Hyun Ma ◽  
Harinarayana Ankamreddy ◽  
Jeong-Oh Shin ◽  
Jae Young Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sonic Hedgehog ◽  
Hair Cells ◽  
Floor Plate ◽  
Basilar Papilla ◽  
Apical Region ◽  
Shh Signaling ◽  
Sensory Hair ◽  
Sensory Hair Cells

Sound frequency discrimination begins at the organ of Corti in mammals and the basilar papilla in birds. Both of these hearing organs are tonotopically organized such that sensory hair cells at the basal (proximal) end respond to high frequency sound, whereas their counterparts at the apex (distal) respond to low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species. In mice, the apical region of the developing cochlea, closer to the ventral midline source of Shh, requires higher levels of Shh signaling than the basal cochlea farther away from the midline. Here, gain-of-function experiments using Shh-soaked beads in ovo or a mouse model expressing constitutively activated Smoothened (transducer of Shh signaling) show up-regulation of apical genes in the basal cochlea, even though these regionally expressed genes are not necessarily conserved between the two species. In chicken, these altered gene expression patterns precede morphological and physiological changes in sensory hair cells that are typically associated with tonotopy such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel, IRK1, which is a bona fide feature of apical hair cells in the basilar papilla. Furthermore, our results suggest that this conserved role of Shh in establishing cochlear tonotopy is initiated early in development by Shh emanating from the notochord and floor plate.

scholarly journals Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 527-540 ◽  
Author(s):  
S. Nery ◽  
H. Wichterle ◽  
G. Fishell
Keyword(s):  
Sonic Hedgehog ◽  
Retroviral Vectors ◽  
Medial Ganglionic Eminence ◽  
Wild Type ◽  
Ganglionic Eminence ◽  
Early Expression ◽  
Pdgfr Alpha

This study addresses the role of Sonic hedgehog (Shh) in promoting the generation of oligodendrocytes in the mouse telencephalon. We show that in the forebrain, expression of the early oligodendrocyte markers Olig2, plp/dm20 and PDGFR(alpha) corresponds to regions of Shh expression. To directly test if Shh can induce the development of oligodendrocytes within the telencephalon, we use retroviral vectors to ectopically express Shh within the mouse embryonic telencephalon. We find that infections with Shh-expressing retrovirus at embryonic day 9.5, result in ectopic Olig2 and PDGFR(alpha) expression by mid-embryogenesis. By postnatal day 21, cells expressing ectopic Shh overwhelmingly adopt an oligodendrocyte identity. To determine if the loss of telencephalic Shh correspondingly results in the loss of oligodendrocyte production, we studied Nkx2.1 mutant mice in which telencephalic expression of Shh is selectively lost. In accordance with Shh playing a role in oligodendrogenesis, within the medial ganglionic eminence of Nkx2.1 mutants, the early expression of PDGFR(alpha) is absent and the level of Olig2 expression is diminished in this region. In addition, in these same mutants, expression of both Shh and plp/dm20 is lost in the hypothalamus. Notably, in the prospective amygdala region where Shh expression persists in the Nkx2.1 mutant, the presence of plp/dm20 is unperturbed. Further supporting the idea that Shh is required for the in vivo establishment of early oligodendrocyte populations, expression of PDGFR(alpha) can be partially rescued by virally mediated expression of Shh in the Nkx2.1 mutant telencephalon. Interestingly, despite the apparent requirement for Shh for oligodendrocyte specification in vivo, all regions of either wild-type or Nkx2.1 mutant telencephalon are competent to produce oligodendrocytes in vitro. Furthermore, analysis of CNS tissue from Shh null animals definitively shows that, in vitro, Shh is not required for the generation of oligodendrocytes. We propose that oligodendrocyte specification is negatively regulated in vivo and that Shh generates oligodendrocytes by overcoming this inhibition. Furthermore, it appears that a Shh-independent pathway for generating oligodendrocytes exists.

Zebrafishsmoothenedfunctions in ventral neural tube specification and axon tract formation

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3497-3509 ◽  
Author(s):  
Zoltán M. Varga ◽  
Angel Amores ◽  
Katharine E. Lewis ◽  
Yi-Lin Yan ◽  
John H. Postlethwait ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Floor Plate ◽  
Slow Muscle ◽  
Pituitary Cells ◽  
Shh Signaling ◽  
Ventral Neural Tube ◽  
Hypothalamic Cells

Sonic hedgehog (Shh) signaling patterns many vertebrate tissues. shh mutations dramatically affect mouse ventral forebrain and floor plate but produce minor defects in zebrafish. Zebrafish have two mammalian Shh orthologs, sonic hedgehog and tiggy-winkle hedgehog, and another gene, echidna hedgehog, that could have overlapping functions. To examine the role of Hedgehog signaling in zebrafish, we have characterized slow muscle omitted (smu) mutants. We show that smu encodes a zebrafish ortholog of Smoothened that transduces Hedgehog signals. Zebrafish smoothened is expressed maternally and zygotically and supports specification of motoneurons, pituitary cells and ventral forebrain. We propose that smoothened is required for induction of lateral floor plate and a subpopulation of hypothalamic cells and for maintenance of medial floor plate and hypothalamic cells.

Looking Backward to Move Forward

2017 ◽  
Vol 43 (4) ◽  
pp. 555-569 ◽  
Author(s):  
Boaz Hameiri ◽  
Arie Nadler
Keyword(s):  
Large Scale ◽  
Field Experiments ◽  
Emotional Needs ◽  
Palestinian Authority ◽  
Mediating Role ◽  
Right Of Return ◽  
Group Members ◽  
The Right ◽  
High Level

Two large-scale surveys conducted in Israel (Study 1A) and the Palestinian Authority (Study 1B) show that the belief by group members that people in the “enemy” group acknowledge their victimhood (i.e., Holocaust and Nakba for Jews and Palestinians, respectively) is associated with Israeli-Jews’ readiness to accept responsibility for Palestinian sufferings and offer apologies. For Palestinians, this belief is linked to a perceived higher likelihood of a reconciled future with Israelis. Three field experiments demonstrate that a manipulated high level of acknowledgment of Jewish victimhood by Palestinians (Studies 2 and 4) and of Palestinian victimhood by Israeli-Jews (Study 3) caused greater readiness to make concessions for the sake of peace on divisive issues (e.g., Jerusalem, the 1967 borders, the right of return) and increased conciliatory attitudes. Additional analyses indicate the mediating role of increased trust and reduced emotional needs in these relationships.

scholarly journals Role of the Agrobacterium tumefaciens VirD2 Protein in T-DNA Transfer and Integration

1998 ◽  
Vol 11 (7) ◽  
pp. 668-683 ◽  
Author(s):  
Kirankumar S. Mysore ◽  
Burgund Bassuner ◽  
Xiao-bing Deng ◽  
Nune S. Darbinian ◽  
Andrei Motchoulski ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Fusion Protein ◽  
Binary Vector ◽  
Type A ◽  
Blue Staining ◽  
Wild Type ◽  
Dna Integration ◽  
Right Border ◽  
The Right

VirD2 is one of the key Agrobacterium tumefaciens proteins involved in T-DNA processing and transfer. In addition to its endonuclease domain, VirD2 contains a bipartite C-terminal nuclear localization sequence (NLS) and a conserved region called ω that is important for virulence. Previous results from our laboratory indicated that the C-terminal, bipartite NLS and the ω region are not essential for nuclear uptake of T-DNA, and further suggested that the ω domain may be required for efficient integration of T-DNA into the plant genome. In this study, we took two approaches to investigate the importance of the ω domain in T-DNA integration. Using the first approach, we constructed a T-DNA binary vector containing a promoterless gusA-intron gene just inside the right T-DNA border. The expression of β-glucuronidase (GUS) activity in plant cells transformed by this T-DNA would indicate that the T-DNA integrated downstream of a plant promoter. Approximately 0.4% of the tobacco cell clusters infected by a wild-type A. tumefaciens strain harboring this vector stained blue with 5-bromo-4-chloro-3-indolyl β-d-glucuronic acid (X-gluc). However, using an ω-mutant A. tumefaciens strain harboring the same binary vector, we did not detect any blue staining. Using the second approach, we directly demonstrated that more T-DNA is integrated into high-molecular-weight plant DNA after infection of Arabidopsis thaliana cells with a wild-type A. tumefaciens strain than with a strain containing a VirD2 ω deletion/substitution. Taken together, these data indicate that the VirD2 ω domain is important for efficient T-DNA integration. To determine whether the use of the T-DNA right border is altered in those few tumors generated by A. tumefaciens strains harboring the ω mutation, we analyzed DNA extracted from these tumors. Our data indicate that the right border was used to integrate the T-DNA in a similar manner regardless of whether the VirD2 protein encoded by the inciting A. tumefaciens was wild-type or contained an ω mutation. In addition, a mutant VirD2 protein lacking the ω domain was as least as active in cleaving a T-DNA border in vitro as was the wild-type protein. Finally, we investigated the role of various amino acids of the ω and bipartite NLS domains in the targeting of a GUS-VirD2 fusion protein to the nucleus of electroporated tobacco protoplasts. Deletion of the ω domain, or mutation of the 10-amino-acid region between the two components of the bipartite NLS, had little effect upon the nuclear targeting of the GUS-VirD2 fusion protein. Mutation of both components of the NLS reduced, but did not eliminate, targeting of the fusion protein to the nucleus.

The right word in the left place

2012 ◽  
Vol 2 (2) ◽  
pp. 273-300 ◽  
Author(s):  
Dmitrii Yurievich Manin
Keyword(s):  
Empirical Study ◽  
Large Scale ◽  
Literary Texts ◽  
Web Based ◽  
Avant Garde ◽  
The Right ◽  
Traditional Poetry ◽  
Formal Constraints

This work describes a large-scale empirical study that quantifies two aspects of lexical foregrounding in literary texts: the unpredictability (unexpectedness) and constrainedness (irreplaceability) of individual words in context. The data are generated by a Web-based literary game where players guess words in fragments of real texts. The results shed new light on the nature of the distinction between poetry and prose and on the role of formal constraints in poetry. In particular, traditional poetry tends to have higher constrainedness than prose and comparable unpredictability, while avant-garde poetry is characterized by higher unpredictability than prose and comparable constrainedness.

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