Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ECTODERMAL DEFECT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed1987

Carrageenan induces anomalies in the chick embryo. A light microscopic study.

Chick embryos injected with lambda-carrageenan prior to incubation and studied with light microscopy at 48 hours of development presented various anomalies. Lack of closure at different levels of the neural tube was one of the lesions most frequently seen. Rachischisis and craniorachischisis were commonly associated with various degrees of hyperplasia of the neural tube wall. Diverse patterns of neural hyperplasia ranged from total occlusion of the neural tube to localized thickening of lateral walls leading to a typical "hourglass" appearance of the ependymal lumen. Multiple septa and cavitations of the neural tube lumen were also recorded. Cephalic and/or trunk duplication of the body as well as disorganization of notochord and somites were frequently associated with rachischisis and areas of necrosis or pyknosis of neural tissue. Neural crest cells, which are normally present in paraneural areas at the stages studied, were not encountered in the carrageenan-injected embryos. These areas were frequently occupied by hyperplastic ectodermic folds. Similarity of present findings on carrageenan-treated embryos with the anomalies induced by selective destruction or impairment of migration of neural crest cells suggests that involvement of this cell population may have a role in the causation of the anomalies observed.

Animals↗
PubMed2004

Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease.

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.

Journal Article↗
PubMedDate not supplied

[Goltz syndrome].

Goltz syndrome or focal dermal hypoplasia is a hereditary disorder, is a rare mesodermal hypoplasia found primarily in females. It is characterized by linear hypoplasia of the skin and tumors of fat or lipomatous lesions. There are significant defects of the skeleton, dental structures, eyes, soft tissues and skin. In our work an example of new-born female with this syndrome is reported, and a review of 136 cases from the literature is presented.

Child, Preschool↗
PubMed2001

Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts.

Establishing cellular polarity is critical for tissue organization and function. Initially discovered in the landmark genetic screen for Drosophila developmental mutants, bazooka, crumbs, shotgun and stardust mutants exhibit severe disruption in apicobasal polarity in embryonic epithelia, resulting in multilayered epithelia, tissue disintegration, and defects in cuticle formation. Here we report that stardust encodes single PDZ domain MAGUK (membrane-associated guanylate kinase) proteins that are expressed in all primary embryonic epithelia from the onset of gastrulation. Stardust colocalizes with Crumbs at the apicolateral boundary, although their expression patterns in sensory organs differ. Stardust binds to the carboxy terminus of Crumbs in vitro, and Stardust and Crumbs are mutually dependent in their stability, localization and function in controlling the apicobasal polarity of epithelial cells. However, for the subset of ectodermal cells that delaminate and form neuroblasts, their polarity requires the function of Bazooka, but not of Stardust or Crumbs.

Adherens Junctions↗
PubMed2006

Incontinentia pigmenti: clinical observation of 40 Korean cases.

Incontinentia pigmenti (IP) is an uncommon genodermatosis that usually occurs in female infants. It is characterized by ectodermal, mesodermal, neurological, ocular, and dental manifestations. The aim of this study was to clarify clinical symptoms, accompanying diseases, and complications of IP. Forty cases of IP have been reviewed by their medical records, laboratory data, clinical photographs, and telephone survey. Male-to-female ratio was 1 to 19 and their onsets were mostly in utero. They were usually diagnosed during the neonatal period owing to their early expression of skin manifestation. Central nervous system anomalies were found in 46.7%. Ocular disorders and dental defects were detected in 66.7% and 72.7% respectively. The most commonly diagnosed anomalies were hypodontia, retinopathy, and seizure. For better understanding of IP, long term and close cooperation between dermatologists, pediatricians, neuroscientists, genetic counselors, and even dentists is crucial.

Central Nervous System Diseases↗
PubMed1998

Gene defect behind APECED: a new clue to autoimmunity.

The molecular background of human autoimmunity is poorly understood. Although many autoimmune diseases have a genetic basis, the actual disease appearance results from a complex interplay between genes and environment and thus these diseases represent typical multifactorial diseases. Even with molecular tools provided by the Human Genome Project, it still remains a challenge to identify the predisposing DNA variants behind such multifactorial traits. Two strategies have been suggested to provide short-cuts to the dissection of the genetic background of complex autoimmune diseases: (i) identification of genes in rare human diseases with a strong autoimmune component or (ii) unravelling loci causing phenotypes resembling autoimmune diseases in inbred mice strains. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autosomal disease with a recessive inheritance pattern, characterized by multiple autoimmune endocrinopathies, chronic mucocutaneous candidiasis and ectodermal dystrophies. Since it is the only known human autoimmune disease inherited in a Mendelian fashion, it provides an excellent model to analyse the genetic component of human autoimmunity. The causative gene for APECED was isolated recently by a traditional positional cloning strategy by two independent groups. The cDNA for the APECED gene proved to originate from a novel gene, AIRE , which is expressed prevalently in thymus, pancreas and adrenal cortex. Multiple mutations in AIRE have been identified in APECED patients. The predicted proline-rich AIRE polypeptide harbours two PHD-type zinc finger motifs and contains a putative nuclear targeting signal suggesting its involvement in the regulation of transcription. In the future, functional analysis of the AIRE protein both in vitro and in vivo will provide valuable insight not only into the molecular pathogenesis of APECED but also into the aetiology of autoimmunity in general.

Animals↗
PubMedDate not supplied

[The morphogenesis of the human brain on the 27th-35th day of development with disordered neurulation].

Human embryos with anomalies of brain and spinal cord were studied on 27-35th day of the development. It was established that developmental anomalies were associated with the disturbed formation of neural tube. The reconstruction of three-dimensional brain arrangement of embryos has shown the presence of different variants of nonclosed medullar tori. In mild disturbance of neurulation, there is an acceleration of organogenesis and morphological differentiation induced by the shackening of normal mechanical tensions and relaxation of neuroepithelial layers. In presence of substantial parts of open neural tube, the development of brain and ectodermal derivatives becomes disturbed to be a possible cause of anencephaly and hypotelorism. The type of disturbed neurulation inducing developmental anomalies of nervous system is suggested to be a factor which determines forms of secondary craniofacial and cranial pathology.

Abortion, Spontaneous↗
PubMed1991

Pathogenesis of limb malformations in mice induced by methoxyacetic acid.

The present study was performed to reveal the pathogenesis of limb malformations induced by methoxyacetic acid (MAA) in developing mouse limbs. Pregnant Jcl:ICR mice were orally given at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Various patterns of cell death in limb buds were observed by vital dye staining with Nile blue A. Under a light microscope and transmission electron microscope, excessive cell death was observed in the mesenchyme as well as in the apical ectodermal ridge (AER) 2 hr after MAA treatment, reaching a maximum after 6 hr. Scanning electron microscopic examinations showed hypoplasia of the AER and small hand plates 24 hr after treatment. Small hand plates and delayed digital ray formation were noted at 48 hr. Neither detachment nor massive necrosis was detected in the periderm covering the limb bud. The distribution of cell death 6 hr after treatment was similar in limb buds treated either at gd 10.5, 11.0 or 11.5, but the final pattern of limb defects was different in fetuses treated at different stages. This study indicates that variations in the pattern of limb defects induced by MAA are due to differences in the amount and distribution of cell death, together with differences in the regenerative capacity of surviving cells.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Mesodermal induction defect as a possible cause of ear malformations.

Deafness due to inner ear anomalies is rarely associated with malformations of the auricles. We describe two brothers with profound congenital sensorineural deafness, abnormal vestibular function, normal ossicles, and delayed motor development. Since the external and inner ear originate from distinctly separate structures, the embryogenesis of this malformation association is less clear than in the more common association of external and middle anomalies, where the latter two structures are derived from the first and second branchial arches. The combination of auricular and inner ear anomalies, with sparing of the middle ear structures, can be explained on the assumption that mesodermal induction is responsible for normal differentiation of both the otocyst and of the branchial arch ectoderm. A recessive mutant gene may lead to a deficiency of a mesodermal inducer substance of a target tissue receptor site. A similar mechanism may be involved in other multiple malformation syndromes, whereby a mutant gene acting during a specific period of organogenesis causes disruption of the normal induction-competence relationship.

Cell Differentiation↗
PubMed2000

Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.

Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL-deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes-both of ectodermal origin-are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL-deficient mice is reminiscent of the spontaneous mouse mutant furless (fs). Analyses of the ctsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis and regular hair follicle morphogenesis and cycling.

Alopecia↗
PubMed1999

EGF signalling regulates cell invagination as well as cell migration during formation of tracheal system in Drosophila.

The Drosophila tracheal system is a network of epithelial tubes that arises from the tracheal placodes, lateral clusters of ectodermal cells in ten embryonic segments. The cells of each cluster invaginate and subsequent formation of the tracheal tree occurs by cell migration and fusion of tracheal branches, without cell division. The combined action of the Decapentaplegic (Dpp), Epidermal growth factor (EGF) and breathless/branchless pathways are thought to be responsible for the pattern of tracheal branches. We ask how these transduction pathways regulate cell migration and we analyse the consequences on cell behaviour of the Dpp and EGF pathways. We find that rhomboid (rho) mutant embryos display defects not only in tracheal cell migration but also in tracheal cell invagination unveiling a new role for EGF signalling in the formation of the tracheal system. These results indicate that the transduction pathways that control tracheal cell migration are active in different steps of tracheal formation, beginning at invagination. We discuss how the consecutive steps of tracheal morphogenesis might affect the final branching pattern.

Animals↗
PubMed1994

Mesectodermal cell fate analysis in Drosophila midline mutants.

We have used enhancer traps and antibodies as markers of cell identity to assess the relative contribution of individual mesectodermal cell (MEC) lineages to CNS midline morphogenesis in four mutations that disrupt commissure formation in Drosophila. The absence of commissures, leading to longitudinal tract collapse, was seen in embryos mutant for the genes single-minded and slit. MEC lineages did not survive in single-minded mutant embryos, in contrast to the survival of all MEC lineages in slit mutant embryos. The midline glial cells were displaced and appeared ultrastructurally normal in slit mutant embryos, yet the presence of the MG was not sufficient to generate commissures. Commissure formation requires correct MEC cytoarchitecture, dependent upon slit activity. In fused commissure mutants (rhomboid and Star) neuron number was reduced in the ventral unpaired median neuron (VUM) lineage and the median neuroblast lineage before commissure formation (stage 12). Subsequent to these neuronal defects, the midline glia died by apoptosis (stage 13). Commissure fusion and glial apoptosis may be triggered by the earlier perturbations in MEC neuronal lineages. These studies establish when the respective activities of each gene are required for the development of each MEC lineage.

Alleles↗
PubMed1976

Senior-Loken syndrome (nephronophthisis and tapeto-retinal degeneration): a study of 8 cases from 5 families.

The association of nephronophthisis and tapeto-retional degeneration was described by both Senior and Loken in 1961, but prior to 1974 only 28 cases had been published. This report describes 8 new cases in 27 members of 5 families. The severe juvenile type produces blindness in infancy and death from renal failure before the age of ten. The adult type is characterized by later onset, slower progression of the renal disease and milder ocular manifestations. The eye disease may be congenital amaurosis of Leber type, pigmentary retinal degeneration or retinitis punctata albescens and the electroretinogram (ERG) is of value in the diagnosis of these varieties of hereditary tapeto-retinal degeneration. Renal involvement is often asymptomatic. Defective urinary concentration leading to polyuria and polydipsia is the earliest sign. Proteinuria is inconstant and urinary sediment is often normal. Two patients had aminoaciduria. The disease progresses inexorably to chronic renal failure. One patient has been successfully transplanted and two others are on chronic hemodialysis. Renal histological changes are those of nephronophthisis with tubulointerstitial lesions and multiple cysts. Senior-Loken syndrome appears to be transmitted by a single autosomal recessive pleotropic gene of variable expression. Degeneration of neuroepithelium and renal tubular epithelium, both tissues of ectodermal origin, may represent a genetically determined enzyme abnormality.

Adolescent↗
PubMed1987

Early-stage developmental abnormalities induced by murine cytomegalovirus.

The onset of the effects of murine cytomegalovirus (MCMV) infection on an early stage of embryonic development (nine days) in a mouse model was studied with the aid of scanning electron microscopy. MCMV was injected into the endometrial lumina of pregnant mice at the time of implantation. The mice were later killed, and sites of embryonic implantation were examined. Compared with uninfected mice and mice inoculated with heat-inactivated virus, litter sizes were reduced, and the incidence of abnormal fetuses was significantly increased among MCMV-infected animals. Scanning electron microscopy also revealed maldeveloped cranial regions characterized by an unclosed neural tube and severely underdeveloped head. Ectodermal abnormalities, including poxlike formations and ballooning cells, were observed in several embryos. Thus, early cytomegalovirus infection may not only result in fetal loss, but may also interfere with the process of morphogenesis.

Animals↗
PubMed1999

Gap junction signalling mediated through connexin-43 is required for chick limb development.

During chick limb development the gap junction protein Connexin-43 (Cx43) is expressed in discrete spatially restricted domains in the apical ectodermal ridge (AER) and mesenchyme of the zone of polarising activity. Antisense oligonucleotides (ODNs) were used to investigate the role of Connexin-43 (Cx43) in the development of the chick limb bud. We have used unmodified ODNs in Pluronic F-127 gel, which is liquid at low temperature but sets at room temperature and so remains situated at the point of application. As a mild surfactant, the gel increases antisense ODN penetration and supplies ODNs to the embryo continually for 12-18 h. We have shown a strong decrease in Cx43 protein expression after application of specific antisense oligonucleotides but the abundance of a closely related protein, Connexin-32 (Cx32), was not affected. Application of antisense Cx43 ODNs at stages 8-15 HH before limb outgrowth resulted in dramatic limb phenotypes. About 40% of treated embryos exhibited defects such as truncation of the limb bud, fragmentation into two or more domains, or complete splitting of the limb bud into two or three branches. Molecular analysis of antisense treated embryos failed to detect Shh or Bmp-2 in anterior structures and suggested that extra lobes seen in nicked and split limbs were not a result of establishment of new signalling centres as found after the application of FGF to the flank. However, examination of markers for the AER showed a number of abnormalities. In severely truncated specimens we were unable to detect the expression of either Fgf-4 or Fgf-8. In both nicked and split limbs the expression of these genes was discontinuous. Down-regulation of Cx43 after the antisense application could be comparable to AER removal and results in distal truncation of the limb bud. Taken together these data suggest the existence of a feedback loop between the FGFs and signalling mediated by Cx43.

Animals↗
PubMed2003

Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation.

The extracellular signal-regulated kinase (ERK) is a component of the mitogen-activated protein kinase cascade. Exon 2 of erk2 was deleted by homologous recombination and resulted in embryonic lethality at embryonic day 6.5. erk2 mutant embryos did not form mesoderm and showed increased apoptosis but comparable levels of BrdUrd incorporation, indicating a defect in differentiation. erk2 null embryonic stem (ES) cells exhibited reduced total ERK activity upon serum stimulation, augmented ERK1 phosphorylation, and decreased downstream p90Rsk phosphorylation and activity; yet ES cell proliferation was unaffected. Mutant ES cells were capable of forming mesoderm; however, treatment of mutant ES cells with the mitogen-activated protein kinase kinase inhibitor PD184352 decreased total ERK activity and expression of the mesodermal marker brachyury, suggesting that ERK1 can compensate for ERK2 in vitro. Normal embryos at embryonic day 6.5 expressed activated ERK1/2 in the extraembryonic ectoderm, whereas erk2 mutant embryos had no detectable activated ERK1/2 in this region, suggesting that activated ERK1 was not expressed, and therefore cannot compensate for loss of ERK2 in vivo. These data indicate that ERK2 plays an essential role in mesoderm differentiation during embryonic development.

Animals↗
PubMed2006

Coexistence of spinal intramedullary teratoma and diastematomyelia in an adult.

STUDY DESIGN: A case report of intramedullary spinal cord teratoma with remote diastematomyelia in a female adult. OBJECTIVE: To present a rare case of a dysembryogenic spinal tumor with concurrent split cord malformation and to define the importance of early surgical removal of the tumor. SETTING: A department of neurosurgery in Greece. METHODS: A 44-year old woman, presented with progressive lower limb muscle weakness, gait disturbances and dysesthesias in the trunk and lower extremity. She underwent plain radiographs, CT and MRI scan, which revealed an exophytic intramedullary spinal cord tumor at the level of T8-T10 and distant diastematomyelia in the upper lumbar spine (L2-L3). She underwent surgical intervention. The tumor was subtotally removed. No attempt was made to treat diastematomyelia. RESULTS: Postoperatively, the patient's neurological status started to improve gradually. After 1 year she exhibited better strength in the lower limb muscles and improved sensation. The histological examination demonstrated mature spinal teratoma consisting of ectodermal, mesodermal and endodermal elements. CONCLUSIONS: In adult patients with intramedullary masses of possible dysembryogenic origin, the whole spine must be examined for additional dysraphic lesions. The choice and the timing of a surgical intervention are strongly dependent on the clinical picture.

Adult↗
PubMed2004

Regulation of eye development by transcription control of CCCTC binding factor (CTCF).

CCCTC binding factor (CTCF), a transcriptional regulator, plays important roles in epigenetics and development. In the present study, we report that overexpression of CTCF in transgenic mice during embryonic development suppresses Pax6 gene expression. This effect causes defects in ocular development that result in microophthalmia. In eye-derived cells transfected with a tetracycline turn-on CTCF system, up-regulation of CTCF expression significantly suppressed Pax6 expression. In contrast, the knockdown of CTCF mRNA resulted in the down-regulation of CTCF protein expression, which in turn enhanced the Pax6 expression. CTCF controls Pax6 transcription by interacting with a repressor element located in the 5'-flanking region upstream of the Pax6 P0 promoter. This interaction suppressed Pax6 gene transcription by blocking the effect of an ectoderm enhancer located 3.5 kb upstream from the P0 promoter. We also found an 80-bp sequence in a region -1.2 kbp upstream from the P0 promoter that contained multiple CTCF binding sites and interacted with nuclear proteins obtained from eye-derived cells forming electrophoretic mobility shift assay complexes with CTCF. We conclude that a novel function of CTCF is to regulate Pax6 transcription by binding to the repressor element, which in turn blocks the effect of the ectoderm enhancer resulting in the inhibition of P0 promoter activity.

Animals↗