Some Questions and Answers About the Role of Hox Temporal Collinearity in Vertebrate Axial Patterning

Author(s):  
A.J.Durston Durston

The vertebrate anterior-posterior (A-P = craniocaudal) axis is evidently made by a timing mechanism. Evidence has accumulated that tentatively identifies the A-P timer as being or involving Hox temporal collinearity. Here, I focus on the two current competing models based on this premise. Common features and points of dissent are examined and a common model is distilled from what remains. This is an attempt to make sense of the literature.

2020 ◽  
Author(s):  
Alejandra C. López-Delgado ◽  
Irene Delgado ◽  
Vanessa Cadenas ◽  
Fátima Sánchez-Cabo ◽  
Miguel Torres

ABSTRACTVertebrate axial skeletal patterning is controlled by coordinated collinear expression of Hox genes and axial level-dependent activity of Hox protein combinations. Transcription factors of the Meis family act as cofactors of Hox proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning have not been established. Similarly, retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however, whether this role is related to Meis/Hox activity in axial patterning remains unknown. Here we study the role of Meis in axial skeleton formation and its relationship to the RA pathway by characterizing Meis1, Meis2 and Raldh2 mutant mice. Meis elimination produces axial skeleton defects without affecting Hox gene transcription, including vertebral homeotic transformations and rib mis-patterning associated to defects in the hypaxial myotome. While Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated to Meis-deficiency and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA positive feedback loop whose output is Meis levels and is essential to establish anterior-posterior identities and pattern of the vertebrate axial skeleton.


Author(s):  
Pierre Pestieau ◽  
Mathieu Lefebvre

This chapter reviews the public health care systems as well as their challenges. It first shows how expenditure on health care has evolved in previous decades and deals with the reasons for the growth observed in almost every European country. It emphasizes the role of technological progress as a main explanatory factor of the increase in medical expenditure but also points to the challenges facing cost-containment policies. Especially, the main common features of health care systems in Europe, such as third-party payment, single provider approach and cost-based reimbursement are discussed. Finally the chapter shows that although inequalities in health exist in the population, health care systems are redistributive. Reforms are thus needed but the trade-off between budgetary efficiency and equity is difficult.


Author(s):  
Dorothy Benton ◽  
Eva C Jaeger ◽  
Arielle Kilner ◽  
Ashley Kimble ◽  
Josh Lowry ◽  
...  

Abstract Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. While the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. While depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.


2021 ◽  
Vol 11 (5) ◽  
pp. 632
Author(s):  
Valentina Pacella ◽  
Giuseppe Kenneth Ricciardi ◽  
Silvia Bonadiman ◽  
Elisabetta Verzini ◽  
Federica Faraoni ◽  
...  

The anarchic hand syndrome refers to an inability to control the movements of one’s own hand, which acts as if it has a will of its own. The symptoms may differ depending on whether the brain lesion is anterior, posterior, callosal or subcortical, but the relative classifications are not conclusive. This study investigates the role of white matter disconnections in a patient whose symptoms are inconsistent with the mapping of the lesion site. A repeated neuropsychological investigation was associated with a review of the literature on the topic to identify the frequency of various different symptoms relating to this syndrome. Furthermore, an analysis of the neuroimaging regarding structural connectivity allowed us to investigate the grey matter lesions and white matter disconnections. The results indicated that some of the patient’s symptoms were associated with structures that, although not directly damaged, were dysfunctional due to a disconnection in their networks. This suggests that the anarchic hand may be considered as a disconnection syndrome involving the integration of multiple antero-posterior, insular and interhemispheric networks. In order to comprehend this rare syndrome better, the clinical and neuroimaging data need to be integrated with the clinical reports available in the literature on this topic.


Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 139-149 ◽  
Author(s):  
S.L. Ang ◽  
J. Rossant

We have developed germ layer explant culture assays to study the role of mesoderm in anterior-posterior (A-P) patterning of the mouse neural plate. Using isolated explants of ectodermal tissue alone, we have demonstrated that the expression of Engrailed-1 (En-1) and En-2 genes in ectoderm is independent of mesoderm by the mid- to late streak stage, at least 12 hours before their onset of expression in the neural tube in vivo at the early somite stage. In recombination explants, anterior mesendoderm from headfold stage embryos induces the expression of En-1 and En-2 in pre- to early streak ectoderm and in posterior ectoderm from headfold stage embryos. In contrast, posterior mesendoderm from embryos of the same stage does not induce En genes in pre- to early streak ectoderm but is able to induce expression of a general neural marker, neurofilament 160 × 10(3) M(r). These results provide the first direct evidence for a role of mesendoderm in induction and regionalization of neural tissue in mouse.


2012 ◽  
Vol 13 (2) ◽  
pp. 37-59
Author(s):  
Karen Newman

Cross-national distances between national cultures and national institutions have been studied extensively in the last two decades, particularly with respect to their effects on the conduct of international business. Yet varying levels of analysis, inconsistent definitions, and different operationalizations of cross-national distances inhibit theoretical and empirical advances. Three approaches to non-geographic cross-national distance permeate the literature: psychic distance, national cultural distance, and institutional distance. The meaning of psychic distance has become muddied by evolving operationalizations, from objective indicators to individual perceptions. National cultural distance has been confused with both psychic distance and institutional distance. Various and inconsistent institutional arrangements and business practices are used as measures of institutional distance. This article reviews overlaps, inconsistencies, and ambiguities in the definitions and measurements of psychic, national cultural and institutional distance; suggests a way to rationalize the three constructs; and offers two competing models to explain the role of all three distances in international business decisions.


Author(s):  
Rohit Joshi ◽  
Rashmi Sipani ◽  
Asif Bakshi

Hox genes have been known for specifying the anterior-posterior axis (AP) in bilaterian body plans. Studies in vertebrates have shown their importance in developing region-specific neural circuitry and diversifying motor neuron pools. In Drosophila, they are instrumental for segment-specific neurogenesis and myogenesis early in development. Their robust expression in differentiated neurons implied their role in assembling region-specific neuromuscular networks. In the last decade, studies in Drosophila have unequivocally established that Hox genes go beyond their conventional functions of generating cellular diversity along the AP axis of the developing central nervous system. These roles range from establishing and maintaining the neuromuscular networks to controlling their function by regulating the motor neuron morphology and neurophysiology, thereby directly impacting the behavior. Here we summarize the limited knowledge on the role of Drosophila Hox genes in the assembly of region-specific neuromuscular networks and their effect on associated behavior.


Author(s):  
Aleksei V. Makarychev

The article is devoted to the study of the “Shakespearean text” by Yuri Dombrovsky from the standpoint of Bakhtin dialogism. Clarifies the concept of “Shakespearean text” refers to and analyzes “Shakespearean text” by Dombrovsky, including artistic works – a trilogy of novels about Shakespeare (“Dark Lady” “Second-highest quality bed”, “Royal Rescript”) and two chapters of the novel “Dark Lady” (“Queen” and “Count Essex”), originally entered into its composition, but later was published separately, as well as two scientific and critical articles – “‘RetlandBaconSouthamptonShakespeare’: about the myth, anti-myth and biographical hypothesis” and “To Italians about Shakespeare”. The study author states that “Shakespearean text” by Yuri Dombrovsky dominated themes of tyranny and government that does not want to hear the people, of censorship, depriving the artist’s freedom of expression and the role of the artist in an unfree society. Special attention is paid to the problem of interaction between Shakespeare and monologue-authoritarian society in the artistic world created by the writer. The author hypothesizes that in the trilogy of short stories about Shakespeare, Dombrovsky addressed such problems of the totalitarian regime as censorship, cruelty and despotism of power from a relatively “safe” distance – the age of Shakespeare. The author notes the presence of a special situation of double dialogue in “Shakespearean text” by Yuri Dombrovsky: the dialogue is conducted through the Shakespearean era with the contemporary writer’s reality, power and culture. The article proves the similarity of Dombrovsky as a biographical author with the Shakespeare he portrayed, and notes the presence of common features in both writers (sacralization of creativity, impulsive character, addiction to alcohol, epileptic seizures, etc.). The conducted research allows us to conclude that Dombrovsky, attempting a dialogue with the monologue-authoritarian power, finds a voice through art, like “his” Shakespeare. Dombrovsky connects the ways of solving the problem of the artist and power with art as the only way to build a dialogue in the conditions of totalitarianism – not so much with the authorities, who are not able to hear it, as with themselves.


2018 ◽  
Author(s):  
Xiao-Yong Li ◽  
Michael B. Eisen

AbstractThe maternal factor Zelda is broadly bound to zygotic enhancers during early fly embryogenesis, and has been shown to be important for the expression of a large number of genes. However, its function remains poorly understood. Here, we carried out detailed analysis of the functional role of Zelda on the activities of a group of enhancers that drive patterned gene expression along the anterior -posterior axis. We found that among these enhancers, only one lost its activity entirely when all its Zelda bind sites were mutated. For all others, mutations of all of their Zelda binding sites only had limited effect, which varied temporally and spatially. These results suggest that Zld may exert a quantitative effect on a broad range of enhancers, which presumably is critical to generate highly diverse spatial and temporal expression patterns for different genes in the developmental gene network in fly embryo. Lastly, we found that the observed effect of Zelda site mutations was much stronger when a mutant enhancer was tested using a BAC based reporter construct than a simple reporter construct, suggesting that the effect of Zld is dependent on chromatin environment.


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