scholarly journals Abnormal Epidermal Keratinization in the repeated epilation mutant mouse

1982 ◽  
Vol 92 (2) ◽  
pp. 387-397 ◽  
Author(s):  
KA Holbrook ◽  
BA Dale ◽  
KS Brown

Repeated epilation (Er) is a radiation-induced, autosomal, incomplete dominant mutation in mice which is expressed in heterozygotes but is lethal in the homozygous condition. Many effects of the mutation occur in skin: the epidermis in Er/Er mice is adhesive (oral and nasal orifices fuse, limbs adhere to the body wall), hyperplastic, and fails to undergo terminal differentiation. Skin from fetal +/+, Er/+ and Er/Er mice at ages pre- and postkeratinization examined by light, scanning, and transmission electron microscopy showed marked abnormalities in tissue architecture, differentiation, and cell structure; light and dark basal epidermal cells were separated by wide intercellular spaces, joined by few desmosomes, and contained phagolysomes. The numbers of spinous, granular, and superficial layers were highly variable within any given region and among various regions of the body. In some areas, 2-8 layers of granular cells, containing large or diminutive keratohyalin granules, extended to the epidermal surface; in others, the granular layers were covered by several layers of partially keratinized or nonkeratinized cells. In rare instances, a single or small group of cornified cells was present among the granular layers but was not associated with the epidermal surface. Both the granular and nonkeratinized/partially keratinized upper epidermal layers Er/Er skin gave positive immunofluorescence with antiserum to the histidine-rich, basic protein, filaggrin. Proteins in epidermal extracts from +/+, Er/+ and Er/Er mice were separated and identified by radio- and immunolabeling techniques. The Er/Er extract was missing a 26.5- kdalton protein and had an altered ratio of bands in the keratin region. The 26.5-kdalton band was histidine-rich and cross-reacted with the antiserum to rat filaggrin. Several high molecular weight bands present in both Er/Er and +/+ extracts also reacted with the antiserum. These are presumed to be the precursors of filaggrin and to account for the immunofluorescence om Er/Er epidermis even though the product protein is absent. The morphologic and biochemical data indicated that the genetic defect has a general and profound influence on epidermal differentiation, including alteration of two proteins (filaggrin and keratin) important in normal terminal differentiation, tissue architecture, and cytology. Identification of epidermal abnormalities at early stages of development (prekeratinization) and defective structure of other tissues and gross anatomy suggest that the mutation is responsible for a defect in same regulatory step important in many processes of differentiation and development.

2006 ◽  
Vol 309-311 ◽  
pp. 1023-1026
Author(s):  
E.T. Uzumaki ◽  
C.S. Lambert

In this study, porous bioceramics (titanium foam with diamond-like carbon coatings, glass foam and zirconium oxide foam) were produced using expansion in vacuum. The porosity, the pore size and pore morphology can be adjusted in agreement with the application. The different 3D structures were obtained by varying the parameters of the process. The microstructure and morphology of the porous materials were observed by scanning electron microscopy (SEM) and optical microscopy. The foam exhibit an open-cell structure with interconnected macropores, which provide the potential for tissue ingrowths and the transport of the body fluids.


1993 ◽  
Vol 13 (12) ◽  
pp. 7793-7801
Author(s):  
R J Lake ◽  
W R Jelinek

We determined the nucleotide sequence of a mouse and a human cDNA, which we designate STPK13, that encodes an apparent protein kinase related to that encoded by the Drosophila melanogaster polo gene and the Saccharomyces cerevisiae CDC5 gene. The polo and CDC5 gene products are required for normal mitosis. The STPK13 mRNA is regulated during terminal erythrodifferentiation and during the cell cycle. Within the precommitment period of murine erythroleukemia cell terminal differentiation, most of the poly(A) tail is lost from the STPK13 mRNA, but the body of the mRNA remains unchanged in abundance; this poly(A) loss does not occur in mutant erythroleukemia cells that fail to commit to terminal differentiation. During the cell cycle, the abundance of the body of the STPK13 mRNA fluctuates. The mRNA is present in growing but not in nongrowing cells. It reaches a maximum abundance during G2/M phase, is absent or present at only low levels during G1 phase, and begins to reaccumulate at approximately the middle of S phase. The cell cycle-associated accumulation and loss of the STPK13 mRNA could cause a similar fluctuation in abundance of its encoded protein kinase, thereby providing a maximum amount during M phase, when the kinase is thought to function, and little or none at other times of the cell cycle. Posttranscriptional regulation must be responsible for the cell cycle-associated fluctuations because transcription rates are relatively constant during different times of the cell cycle when there are large differences in mRNA abundance.


Parasitology ◽  
2003 ◽  
Vol 126 (3) ◽  
pp. 273-282 ◽  
Author(s):  
M. T. STEWART ◽  
A. MOUSLEY ◽  
B. KOUBKOVÁ ◽  
š. šEBELOVÁ ◽  
N. J. MARKS ◽  
...  

The major muscle systems of the metacercaria of the strigeid trematode, Apatemon cobitidis proterorhini have been examined using phalloidin as a site-specific probe for filamentous actin. Regional differences were evident in the organization of the body wall musculature of the forebody and hindbody, the former comprising outer circular, intermediate longitudinal and inner diagonal fibres, the latter having the inner diagonal fibres replaced with an extra layer of more widely spaced circular muscle. Three orientations of muscle fibres (equatorial, meridional, radial) were discernible in the oral sucker, acetabulum and paired lappets. Large longitudinal extensor and flexor muscles project into the hindbody where they connect to the body wall or end blindly. Innervation to the muscle systems of Apatemon was examined by immunocytochemistry, using antibodies to known myoactive substances: the flatworm FMRFamide-related neuropeptide (FaRP), GYIRFamide, and the biogenic amine, 5-hydroxytryptamine (5-HT). Strong immunostaining for both peptidergic and serotoninergic components was found in the central nervous system and confocal microscopic mapping of the distribution of these neuroactive substances revealed they occupied separate neuronal pathways. In the peripheral nervous system, GYIRFamide-immunoreactivity was extensive and, in particular, associated with the innervation of all attachment structures; serotoninergic fibres, on the other hand, were localized to the oral sucker and pharynx and to regions along the anterior margins of the forebody.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ziguang Lin ◽  
Suoqin Jin ◽  
Jefferson Chen ◽  
Zhuorui Li ◽  
Zhongqi Lin ◽  
...  

Abstract The interfollicular epidermis (IFE) forms a water-tight barrier that is often disrupted in inflammatory skin diseases. During homeostasis, the IFE is replenished by stem cells in the basal layer that differentiate as they migrate toward the skin surface. Conventionally, IFE differentiation is thought to be stepwise as reflected in sharp boundaries between its basal, spinous, granular and cornified layers. The transcription factor GRHL3 regulates IFE differentiation by transcriptionally activating terminal differentiation genes. Here we use single cell RNA-seq to show that murine IFE differentiation is best described as a single step gradualistic process with a large number of transition cells between the basal and spinous layer. RNA-velocity analysis identifies a commitment point that separates the plastic basal and transition cell state from unidirectionally differentiating cells. We also show that in addition to promoting IFE terminal differentiation, GRHL3 is essential for suppressing epidermal stem cell expansion and the emergence of an abnormal stem cell state by suppressing Wnt signaling in stem cells.


2014 ◽  
Vol 94 (4) ◽  
pp. 1287-1312 ◽  
Author(s):  
Stefano Piccolo ◽  
Sirio Dupont ◽  
Michelangelo Cordenonsi

The transcriptional regulators YAP and TAZ are the focus of intense interest given their remarkable biological properties in development, tissue homeostasis and cancer. YAP and TAZ activity is key for the growth of whole organs, for amplification of tissue-specific progenitor cells during tissue renewal and regeneration, and for cell proliferation. In tumors, YAP/TAZ can reprogram cancer cells into cancer stem cells and incite tumor initiation, progression and metastasis. As such, YAP/TAZ are appealing therapeutic targets in cancer and regenerative medicine. Just like the function of YAP/TAZ offers a molecular entry point into the mysteries of tissue biology, their regulation by upstream cues is equally captivating. YAP/TAZ are well known for being the effectors of the Hippo signaling cascade, and mouse mutants in Hippo pathway components display remarkable phenotypes of organ overgrowth, enhanced stem cell content and reduced cellular differentiation. YAP/TAZ are primary sensors of the cell's physical nature, as defined by cell structure, shape and polarity. YAP/TAZ activation also reflects the cell “social” behavior, including cell adhesion and the mechanical signals that the cell receives from tissue architecture and surrounding extracellular matrix (ECM). At the same time, YAP/TAZ entertain relationships with morphogenetic signals, such as Wnt growth factors, and are also regulated by Rho, GPCRs and mevalonate metabolism. YAP/TAZ thus appear at the centerpiece of a signaling nexus by which cells take control of their behavior according to their own shape, spatial location and growth factor context.


2016 ◽  
Vol 3 (1) ◽  
pp. 312-321
Author(s):  
DJ Jordan ◽  
M Griffin ◽  
B Phillips ◽  
S Hindocha ◽  
A Elgawad

Anatomy has long been a topic of interest amongst both those in medicine and those not. The understanding of biology, in terms of the function and structure of the organs and other structures of the body, has dramatically changed over time, and has been closely related to both scientific improvement and religious feeling.There is no doubt that gross anatomy is one of the preclinical cornerstones of medical education, but the way in which it has been taught has changed over the years. As early as the 16thcentury, Vesalius stated that anatomy could only be taught by dissection, however, alternative options for cadaveric study are certainly more available now than when this statement was made.Current teaching methods incorporate the tried and tested cadaveric based dissection, but has more recently been super ceded by the use of computer based imaging and the change to self-orientated or problem based learning. The shift towards the latter has led to a perceived suffering to the gain of anatomical and pathological knowledge of new doctors and surgeons.This paper aims to describe the history of anatomy teaching and review the current evidence for and against the current methods used for its deliverance.


F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1050 ◽  
Author(s):  
Marilyn J. Telen

Although production of hemoglobin S, the genetic defect that causes sickle cell disease (SCD), directly affects only red blood cells, the manifestations of SCD are pervasive, and almost every cell type and organ system in the body can be involved. Today, the vast majority of patients with SCD who receive modern health care reach adulthood thanks to vaccine prophylaxis and improvements in supportive care, including transfusion. However, once patients reach adulthood, they commonly experience recurrent painful vaso-occlusive crises and frequently have widespread end-organ damage and severely shortened life expectancies. Over the last several decades, research has elucidated many of the mechanisms whereby abnormal red blood cells produce such ubiquitous organ damage. With these discoveries have come new ways to measure disease activity. In addition, new pharmaceutical interventions are now being developed to address what has been learned about disease mechanisms.


1992 ◽  
Vol 12 (11) ◽  
pp. 4862-4871
Author(s):  
B J Aneskievich ◽  
E Fuchs

Terminal differentiation of epidermal keratinocytes is inhibited by 1 microM retinoic acid, a concentration which induces differentiation in a number of cell types, including F9 teratocarcinoma cells. The molecular basis for these opposing retinoid responses is unknown, although retinoic acid receptors (RARs) and retinoid X receptors (RXRs) have been detected in both cell types. When F9 cells are stably transfected with a truncated RAR alpha lacking the E/F domain necessary for ligand binding and RAR/RXR dimerization, action at retinoid response elements is suppressed and cells produce a retinoic acid-resistant phenotype; i.e., they are blocked in differentiation (A. S. Espeseth, S. P. Murphy, and E. Linney, Genes Dev. 3:1647-1656, 1989). If retinoid receptors influence epidermal differentiation only in a negative fashion, then suppression of transactivation at retinoid response elements would be expected to enhance, rather than block, keratinocyte differentiation. In this study, we show that surprisingly, even though constitutive expression of an analogous truncated RAR gamma in keratinocytes specifically suppressed transactivation at retinoid response elements, keratinocytes were blocked, rather than enhanced, in their ability to undergo morphological and biochemical features of differentiation. These findings demonstrate a direct and hitherto unrecognized role for RARs and RXRs in positively as well as negatively regulating epidermal differentiation. Additionally, our studies extend those of Espeseth et al. (Genes Dev. 3:1647-1656, 1989), indicating a novel RAR function independent of the E/F domain.


The musculature of the Onychophoran Peripatus dominicae , its ultrastructure and details of innervation are described. Significant differences were noted between its gross anatomy and that reported in previous accounts, notably in the presence of inner circular body wall muscle and a prominent, functionally significant, levator of the leg. The former is important in regard to the evolutionary position of the Onychophora while the latter helps us to understand the control of walking in a lobopodial leg, and therefore the evolution of arthropod locomotion, which was the focus of our interest. Individual muscle fibres are either directly or indirectly attached to the body wall by collagen. There is a small degree of branching of fibres, with or without anastomosis, near their insertions, but most are as long as the muscle of which they are part, and are unbranched except for an occasional thin arm, emerging at an angle, that becomes invaded by collagen fibres and inserts in the skin. Diameters of muscle fibres vary from 1 to 45 pm. They are invaginated by two separate systems of unique wide (0.3 pm) tubules, longitudinal and radial. These are lined with similar material to that forming the basement material of the sarcolemma, and also contain fine strands with collagen-type cross-banding that connect to collagen bundles outside the fibres. In addition there are narrow tubules of ordinary T-tubule diameter. Both wide and narrow tubules make contacts with sarcoplasmic reticulum cysternae. Dense Z bodies are attached to both kinds of wide tubule, to the inside of the sarcolemma, and are scattered, without any obvious array, in the sarcoplasm. Thin myofilaments emerge from the Z bodies parallel to the fibre axis. Thick filaments occur in clusters with a loosely hexagonal array, but without any regular relation to thin ones: relatively few orbits of thin around thick filaments were seen in many muscle fibres regardless of fibre length and conditions during fixation. A unique innervation pattern was found, consisting of a combination of muscle arm to nerve contacts, which appear to be the commonest, and nerve on muscle fibre synapses. At least 13 motor axons were found to supply each small muscle or cluster of muscle fibres in a large muscle. Each muscle arm simultaneously makes synaptic contact with 3 to 7 axons. Nerve on muscle junctions contain from 1 to 8 axons, each making synaptic contacts. The details of the postsynaptic endplate-specializations resemble those seen in mammalian endplates and are markedly different from both arthropod and annelidan neuromuscular synapses.


1859 ◽  
Vol 149 ◽  
pp. 469-477

During the last few years anatomists have considered the muscular substance of the bladder to be composed of elongated contractile fibre-cells, each with a nucleus in it, which possess free ends, and overlap at their pointed extremities without being united or joined together. This notion of the cell-structure originated with Professor Kölliker; and it has since received very general acceptance. From the correctness of that opinion I am led to dissent by my researches; and I purpose to show in this communication to the Royal Society, that both the involuntary muscular tissue of the bladder and the voluntary muscular substance in other parts of the human body have a like composition. In a former paper to the Society (in June 1856) I made the announcement that the views now bought forward of the muscular structure of the bladder were applicable to the involuntary muscular tissue in general; but as my declaration was received with doubt, I determine to withhold its publication until I had been able to repeat my microscopical observations. Before this time I hoped to have completed the task imposed on myself, but occupation has left me leisure enough to examine thoroughly only the muscular structure of the urinary bladder. As my idea is confirmed by the result of the second examination of that viscus, I submit this paper with greater confidence to the consideration researches into the nature of the involuntary muscular tissue in other parts of the body.


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