Pax3 transcripts in melanoblast development Blake, Judith A.; Ziman, Mel R.
Development, growth & differentiation,
December 2005, 2005-Dec, 2005-12-00, 20051201, Volume:
47, Issue:
9
Journal Article
Peer reviewed
Open access
The transcription factor encoded by PAX3 is among the first expressed in the embryo, with a key role in development of the melanocytic lineage. Re‐expression of PAX3, consistently observed in ...cutaneous malignant melanoma (CMM) as compared to normal melanocytes, appears linked to progression of CMM. Previous research has identified PAX3d (encoded by exons 1–9) as the predominant isoform present in CMM, together the with an alternate isoform PAX3c (encoded by exons 1–8). We investigated the expression of Pax3c and Pax3d transcripts during mouse development. The reverse transcription–polymerase chain reaction and immunohistochemistry experiments presented here implicate these transcripts in melanoblast development and demonstrate significant spatial and temporal differences in their expression. Differences in expression were also noted during active hair regrowth in adult skin, which is accompanied by proliferation and migration of melanoblasts into the hair cortex to color new hair. Results indicate that the defined spatial and temporal expression of Pax3d may be linked to either melanoblast proliferation or migration during melanogenesis.
Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. In melanoma, ctDNA has been shown to have clinical ...value as an alternative tumour source for the detection clinically targetable mutations for the assessment of response to therapy. This review provides a critical summary of the evidence that gives credence to the utility of ctDNA as a biomarker for monitoring of disease status in advanced melanoma and the steps required for its implementation into clinical settings.
•ctDNA as a biomarker of disease status in advanced melanoma.•ctDNA as an indicator of response to treatment.•ctDNA for monitoring clonal evolution and emergence of resistance.•Epigenetic changes in melanoma ctDNA.•The challenges associated with clinical implementation of ctDNA for melanoma management.
Studies of the impact of respiratory muscle training (RMT) on central neurodegenerative pathologies have been aimed at improving pulmonary function. However, there is no certainty about the ...effectiveness of RMT in patients affected by these groups of disorders. The purpose of this review was to assess the evidence regarding the efficacy of inspiratory muscle training (IMT) and expiratory muscle training (EMT) on respiratory function in patients with neurodegenerative disorders of the CNS.
A comprehensive search from 1990 to September 2012 on MEDLINE, Physiotherapy Evidence Database (PEDro), PubMed, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases was made. Studies reporting on IMT and EMT in patients with neurodegenerative diseases were included. The selected studies were abstracted using a standardized data collection instrument and were assessed by a quality checklist created and adapted from CONSORT (Consolidated Standards for Reporting Trials) and TREND (Transparent Reporting of Evaluation with Nonrandomized Designs).
Twenty-four studies were identified by the search strategy. Only 19 studies met the criteria for full review. Ten studies met all the inclusion criteria and were included in the final analysis. Of the 16 parameters present in the quality assessment checklist, only six were achieved for the studies analyzed.
There is some evidence that RMT improves a number of respiratory function parameters in patients with Parkinson disease and multiple sclerosis; however, the number of studies and their quality are not sufficient to conclude whether IMT or EMT is effective in improving respiratory function in patients with neurodegenerative disorders of the CNS.
Pax7 encodes a transcription factor well-established as an important determinant of mesencephalic identity and superior collicular development. Pax7 mutant mice, however, present with no obvious ...morphological impairments to the superior colliculus. This finding is paradoxical and has been attributed to functional redundancy afforded by its paralogue Pax3. Here we utilise Pax7 mutant mice to investigate the precise role of this important developmental regulator during superior collicular development and neuronal specification/differentiation. We also assess its spatiotemporal relationship with Pax3 during embryonic development.
Analysis of the superior colliculus of Pax7 mutant and wildtype mice at a variety of developmental timepoints revealed that whilst correct initial specification is maintained, a subpopulation of dorsal mesencephalic neurons is lost at early postnatal stages. Moreover, a comparative analysis of embryonic Pax3 and Pax7 expression profiles indicate that Pax3 expression overlaps extensively with that of Pax7 initially, but their expression domains increasingly diverge as development progresses, coinciding spatiotemporally with neuronal differentiation and maturation of the tissue. Furthermore, Pax3 expression is perturbed within the CNS of embryonic Pax7 mutant mice.
In summary, these results demonstrate that during superior collicular development, Pax7 is required to maintain a subpopulation of dorsal, mesencephalic neurons and partially regulates, spatiotemporally, Pax3 expression within the CNS. The differential nature of Pax7 and Pax3 with respect to neuronal differentiation may have implications for future stem cell therapies aimed at exploiting their developmental capabilities.
Nestin is an intermediate filament protein expressed in dividing cells during the early stages of development in the CNS, PNS and in myogenic and other tissues. Upon differentiation, nestin becomes ...downregulated and is replaced by tissue-specific intermediate filament proteins. Interestingly, nestin expression is reinduced in the adult during pathological situations, such as the formation of the glial scar after CNS injury and during regeneration of injured muscle tissue. Although it is utilised as a marker of proliferating and migrating cells very little is known about its functions or regulation. In depth studies on the distribution and expression of nestin in mitotically active cells indicate a complex role in regulation of the assembly and disassembly of intermediate filaments which together with other structural proteins, participate in remodeling of the cell. The role of nestin in dynamic cells, particularly structural organisation of the cell, appears strictly regulated by phosphorylation, especially its integration into heterogeneous intermediate filaments together with vimentin or alpha-internexin.
Abstract Alveolar rhabdomyosarcoma (ARMS) is a pediatric sarcoma that typically occurs in older children predominantly arising in the trunk and extremities, and exhibits a worse prognosis than other ...types of rhabdomyosarcomas. Most ARMS tumors have t(2; 13) or t(1; 13) translocations, involving PAX3–FKHR and PAX7–FKHR fusion genes, respectively. These genetic events result in a molecular gain of function of the fusion protein which is proposed, in a yet unspecified mechanism, to perturb the differentiation of muscle progenitor cells. While a significant amount of work has been done characterizing PAX–FKHR fusion proteins in ARMS and elucidating their involvement in the sarcomagenic process, their relationship to normal skeletal muscle differentiation remains unestablished. In this manuscript we will explore a potential role for mesenchymal stem cells as the cell of origin of ARMS, and the possibility that PAX–FKHR fusion genes may commit these cells to a myogenic lineage while inhibiting terminal differentiation, thus contributing to ARMS formation. We will also review the structure and function of alternate transcripts of PAX3 , PAX7, FKHR and the fusion genes PAX3–FKHR and PAX7–FKHR, and discuss the role of these genes and their downstream targets in development of ARMS. Additionally, we will review transgenic mouse models and their ability to mimic the formation of ARMS.
Objective:
To examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease.
...Design:
A pilot randomised controlled trial.
Setting:
Home based training program.
Participants:
Eighteen manifest Huntington’s disease patients with a positive genetic test and clinically verified disease expression, were randomly assigned to control group (n=9) and training group (n=9).
Intervention:
Both groups received home-based inspiratory (5 sets of 5 repetitions) and expiratory (5 sets of 5 repetitions) muscle training 6 times a week for 4 months. The control group used a fixed resistance of 9 centimeters of water, and the training group used a progressively increased resistance from 30% to 75% of each patient’s maximum respiratory pressure.
Main measures:
Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minutes walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire were assessed before, at 2 and 4 months after training.
Results:
The magnitude of increases in maximum inspiratory (d=2.9) and expiratory pressures (d=1.5), forced vital capacity (d=0.8), forced expiratory volume in 1 second (d=0.9) and peak expiratory flow (d=0.8) was substantially greater for the training group in comparison to the control group. Changes in swallowing function, dyspnoea and exercise capacity were small (d≤0.5) for both groups without substantial differences between groups.
Conclusions:
A home-based respiratory muscle training program appeared to be beneficial to improve pulmonary function in manifest Huntington’s disease patients but provided small effects on swallowing function, dyspnoea and exercise capacity.
Highlights • Heat stress may be a risk factor for skin carcinogenesis. • Heat activates Heat Shock Proteins (HSPs). • HSPs influence signalling pathways of cell proliferation, survival and apoptosis. ...• Heat stress and UV may synergistically promote transformation of skin cells.
Anxiety and depression are common comorbidities in people diagnosed with chronic obstructive pulmonary disease (COPD). Despite concomitant psychological symptomatology being reported in 22–48% of ...people with COPD, most literature focuses on identifying the risk factors for anxiety or depression separately. Therefore, our objective was to determine whether there is an association between people living with concomitant anxiety and depression and sociodemographic risk factors in people and living with COPD.
This was a cross-sectional study of 242 people living with COPD. Symptomatology of anxiety and depression were assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI-II). Univariate and multivariable logistic regression models were used to test the association between symptomatology and demographic predictor variables. Odds ratios and 95% confidence intervals were derived.
Of the 242 people included, 48.8% (n = 118) had no symptoms of anxiety or depression and 33.5%% (n = 81) had symptomatology for both. Multivariable modelling suggested younger age, having a carer, having a previous psychological medical history, having a higher number of comorbidities and poorer quality of life were associated with concomitant anxiety and depression compared to those without symptomatology.
Further work should be done to build upon our results which adds to the limited literature surrounding risk factors for concomitant psychological symptomatology to facilitate future discussion surrounding reducing these detrimental comorbidities in people with COPD.
•Concomitant anxiety and depression is common in people with COPD.•Risk factors for concomitant psychological symptomatology investigated.•Cross sectional study design using multivariable modelling.•Younger age, having a carer, having a previous psychological medical history, having a higher number of comorbidities and poorer quality of life were found as risk factors.
Pax genes encode a family of transcription factors that have long been recognised as obligate contributors to embryonic development of the CNS, with evidence obtained from various animal models ...illustrating phylogenetically conserved functions. Within the CNS, Pax genes play substantial roles in cellular and regional specification, proliferation, progenitor cell maintenance, anti-apoptosis and neural differentiation. This comprehensive review details the critical functions of those Pax genes involved in pre- and post-natal CNS development, provides possible molecular mechanisms by which Pax genes contribute to proliferation and differentiation of neuronal cells, and explains observed changes in Pax gene expression in response to neurotrauma in the mature animal. Knowledge of the ability of individual Pax genes to specify precise lineages within the CNS is beneficial for cell replacement strategies, particularly in the production of "designer" cells for the treatment of neurodegenerative disorders. The manipulation of stem or committed cells so that they express definitive Pax genes may indeed assist in the pursuit of the holy grail of regenerative medicine - that of CNS cell replacement therapies leading to functional repair. We explain here, however, that only the sophisticated and precise use of Pax genes will lead to a successful outcome.
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