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Results for “ECTODERMAL DEFECT”

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At least 739 records · Page 41Linked to original sources
PubMed1988

Effects of altered expression of the neural cell adhesion molecule, N-CAM, on early neural development in Xenopus embryos.

The neural cell adhesion molecule, N-CAM, is known to be expressed very early in the development of the vertebrate nervous system. In frog embryos, N-CAM expression increases dramatically in ectoderm coincident with the formation of the neural plate and tube, suggesting that morphogenesis of the early nervous system is controlled in part by differential expression of N-CAM. This model was tested by introducing synthetic N-CAM transcripts into Xenopus embryos so that N-CAM was indiscriminately expressed at high levels on the surface of both induced and noninduced ectodermal cells throughout gastrulation and neurulation. Analysis of these embryos shows that high levels of N-CAM misexpression do not effect neural tube formation even though ectopic expression of N-CAM in epidermis and somitic mesoderm caused specific defects in the structure of these tissues. By showing that the properly regulated expression of N-CAM is not essential for neural tube formation, these results provide compelling evidence that N-CAM on its own does not act as a regulatory molecule during early neural development.

Animals↗
PubMed1978

Familial ichthyosis, dwarfism, mental retardation, and renal disease.

The nonrandom association of congenital ichthyosis with neurologic impairment, ectodermal dysplasia, dwarfism, hypogonadism, and renal disease has prompted the review of numerous syndromes. The difficulties in characterization of syndromes in the absence of pathognomonic signs is discussed in relation to three siblings presented herein. Despite extensive investigation, underlying metabolic defects remain obscure.

Adult↗
PubMed1984

Abnormal corneal and eyelid development in the repeated epilation mouse.

Development of the eyelids and cornea in repeated epilation (Er/Er) mice is characterized by fusion of the tarsal conjunctiva to the epithelia of the bulbar conjunctiva and cornea. We investigated the ultrastructural features of this malformation and tested for abnormal expression of filaggrin by immunofluorescence. Heterozygous (Er/+) breeding stock were mated and 13,14,15, and 19-day-old embryos were studied by light and electron microscopy. Fusion occurred in all Er/Er specimens and was associated with abnormal migration of surface ectodermal cells onto the cornea. Immunofluorescence studies with antimouse filaggrin antibody on day 13 and day 15 revealed the presence of filaggrin precursors in the fused epithelia of mutants, but not in normal corneal or conjunctival epithelia. The results suggest defective regulation of the synthesis of cellular proteins and altered cell surface properties in the Er/Er ocular epithelia.

Abnormalities, Multiple↗
PubMed2001

Hair on a gene string: recent advances in understanding the molecular genetics of hair loss.

The hair follicle is finally, after remaining a mystery for many years, beginning to yield some of its molecular secrets. The past decade has seen unprecedented and ever quickening advances in understanding the molecular genetics of the many single gene disorders, which have alopecia as a major feature. This article reviews recent novel clinical and experimental observations, which have shed new light on the basic molecular mechanisms underlying hair morphogenesis, differentiation, keratinization and cycling. We consider recent progress in understanding structural hair defects and complex traits and consider where future developments are likely to occur.

Alopecia↗
PubMed2000

Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens development and differentiation.

Here we report the isolation of a novel forkhead gene, Foxe3, that plays an important role in lens formation. During development Foxe3 is expressed in all undifferentiated lens tissues, and is turned off upon fiber cell differentiation. Foxe3 maps to a chromosomal region containing the dysgenetic lens (dyl) mutation. Mice homozygous for dyl display several defects in lens development. dyl mice also show altered patterns of crystallin expression suggesting a dysregulation of lens differentiation. We have identified mutations in Foxe3 that cosegregate with the dyl phenotype and are a likely cause of the mutant phenotype. Head ectoderm expression of Foxe3 is absent in Rx-/- and Small eye embryos indicating that Rx and Pax6 activity are necessary for Foxe3 expression.

Amino Acid Sequence↗
PubMed1981

Anhidrotic ectodermal dysplasia with transient hypogammaglobulinemia.

An 8-month-old white boy with anhidrotic ectodermal dysplasia (AED) who was referred to the North Carolina Baptist Hospital because of recurrent respiratory infections and hypogammaglobulinemia is presented. His mother had partial expression of AED suggesting x-linked recessive inheritance in this family. She was incidentally given oral glucocorticoids during pregnancy for the treatment of chronic urticaria. The patient's serum immunoglobulins G, A and M were low at 8 months but normal by 15 months of age, and immunologic evaluation failed to show a defect in antibody production or cell-mediated immunity. Although rare, the diagnosis of AED must be considered in infant boys with recurrent fever and respiratory infections. The diagnostic features of the disease may be subtle in young child prior to the eruption of the characteristic peg-shaped teeth.

Agammaglobulinemia↗
PubMed1998

Vinculin knockout results in heart and brain defects during embryonic development.

The vinculin gene codes for a cytoskeletal protein, found in focal adhesion plaques and in cell-cell adherens junctions. Vinculin was inactivated by homologous recombination using a targeting vector in embryonic stem (ES) cells. The heterozygous ES cells were introduced into mice by established procedures to produce heterozygous animals that were normal and fertile. No homozygous vinculin-/- embryos were born and analyses during the gestational period showed that the vinculin null embryos were small and abnormal from day E8 but some survived until E10. The most prominent defect was lack of midline fusion of the rostral neural tube, producing a cranial bilobular appearance and attenuation of cranial and spinal nerve development. Heart development was curtailed at E9.5, with severely reduced and akinetic myocardial and endocardial structures. Mutant embryos were 30-40% smaller, somites and limbs were retarded and ectodermal tissues were sparse and fragile. Fibroblasts (MEF) isolated from mutant embryos were shown to have reduced adhesion to fibronectin, vitronectin, laminin and collagen compared to wild-type levels. In addition, migration rates over these substrata were two-fold higher and the level of focal adhesion kinase (FAK) activity was three-fold higher. We conclude that vinculin is necessary for normal embryonic development, probably because of its role in the regulation of cell adhesion and locomotion, cell behaviors essential for normal embryonic morphogenesis, although specific roles in neural and cardiac development cannot be ruled out.

Animals↗
PubMed1998

Pten is essential for embryonic development and tumour suppression.

The PTEN gene encodes a dual-specificity phosphatase mutated in a variety of human cancers. PTEN germline mutations are found in three related human autosomal dominant disorders, Cowden disease (CD), Lhermitte-Duclos disease (LDD) and Bannayan-Zonana syndrome (BZS), characterized by tumour susceptibility and developmental defects. To examine the role of PTEN in ontogenesis and tumour suppression, we disrupted mouse Pten by homologous recombination. Pten inactivation resulted in early embryonic lethality. Pten-/- ES cells formed aberrant embryoid bodies and displayed an altered ability to differentiate into endodermal, ectodermal and mesodermal derivatives. Pten+/- mice and chimaeric mice derived from Pten+/- ES cells showed hyperplastic-dysplastic changes in the prostate, skin and colon, which are characteristic of CD, LDD and BZS. They also spontaneously developed germ cell, gonadostromal, thyroid and colon tumours. In addition, Pten inactivation enhanced the ability of ES cells to generate tumours in nude and syngeneic mice, due to increased anchorage-independent growth and aberrant differentiation. These results support the notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis, and demonstrate that Pten is a tumour suppressor essential for embryonic development.

Adenocarcinoma↗
PubMed2005

Exploiting the keratin 17 gene promoter to visualize live cells in epithelial appendages of mice.

Keratin genes afford, given their large number (>50) and differential regulation, a unique opportunity to study the mechanisms underlying specification and differentiation in epithelia of higher metazoans. Moreover, the small size and regulation in cis of many keratin genes enable the use of their regulatory sequence to achieve targeted gene expression in mice. Here we show that 2 kilobases of 5' upstream region from the mouse keratin 17 gene (mK17) confers expression of green fluorescent protein (GFP) in major epithelial appendages of transgenic mice. Like that of mK17, onset of [mK17 5']-GFP reporter expression coincides with the appearance of ectoderm-derived epithelial appendages during embryonic development. In adult mice, [mK17 5']-GFP is appropriately regulated within hair, nail, glands, and oral papilla. Tracking of GFP fluorescence allows for the visualization of growth cycle-related changes in hair follicles, and the defects engendered by the hairless mutation, in live skin tissue. Deletion of an internal 48-bp interval, which encompasses a Gli-responsive element, from this promoter results in loss of GFP fluorescence in most appendages in vivo, suggesting that sonic hedgehog participates in K17 regulation. The compact mK17 gene promoter provides a novel tool for appendage-preferred gene expression and manipulation in transgenic mice.

Animals↗
PubMed2000

Imaging patterns of calcium transients during neural induction in Xenopus laevis embryos.

Through the injection of f-aequorin (a calcium-sensitive bioluminescent reporter) into the dorsal micromeres of 8-cell stage Xenopus laevis embryos, and the use of a Photon Imaging Microscope, distinct patterns of calcium signalling were visualised during the gastrulation period. We present results to show that localised domains of elevated calcium were observed exclusively in the anterior dorsal part of the ectoderm, and that these transients increased in number and amplitude between stages 9 to 11, just prior to the onset of neural induction. During this time, however, no increase in cytosolic free calcium was observed in the ventral ectoderm, mesoderm or endoderm. The origin and role of these dorsal calcium-signalling patterns were also investigated. Calcium transients require the presence of functional L-type voltage-sensitive calcium channels. Inhibition of channel activation from stages 8 to 14 with the specific antagonist R(+)BayK 8644 led to a complete inhibition of the calcium transients during gastrulation and resulted in severe defects in the subsequent formation of the anterior nervous system. BayK treatment also led to a reduction in the expression of Zic3 and geminin in whole embryos, and of NCAM in noggin-treated animal caps. The possible role of calcium transients in regulating developmental gene expression is discussed.

Aequorin↗
PubMed2005

X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness.

X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm-derived tissues. Although EDA function in skin appendage development has been studied in Eda mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) >80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-kappaB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease.

Animals↗
PubMed2003

Tetraploid embryos rescue the early defects of tw5/tw5 mouse embryos.

tclw5 is a t-complex recessive lethal mutation of the tw5-haplotype. Since tw5/tw5 embryos die soon after implantation, the tclw5 gene is thought to play an important role in early embryogenesis. Previous histological studies have demonstrated that tw5 homozygotes do not survive past the gastrulation stage due to extensive death of the embryonic ectoderm, whereas the extraembryonic tissues were less affected. In the present study, we demonstrate that tw5/tw5 embryos may be distinguished from wildtype littermates at embryonic (E) day 5.5. At this stage, the visceral endoderm of tw5/tw5 embryos appeared to be different, possessing smaller and fewer vacuoles compared to normal littermates. This led us to hypothesize that the visceral endoderm may be affected by tclw5. Confirmation was provided by the rescue of tw5/tw5 embryos following aggregation with tetraploid embryos. However, rescued embryos did not survive past E9.0 and displayed an underdeveloped posterior region. This would indicate that the actions of tclw5 extend beyond the midgestation stage.

Animals↗
PubMed2005

JNK and ROKalpha function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements.

The Wnt/planar cell polarity (PCP) pathway plays a critical role in wing, eye, and sensory bristle development of Drosophila and in convergent extension (CE) movements during vertebrate gastrulation. In Drosophila, Jun N-terminal kinase (JNK) and Rho-associated kinase (ROK) participate in RhoA-mediated PCP pathway during eye and wing development. In mammalian cells, Rac1 and Cdc42 but not RhoA are required for JNK activation by Wnt/PCP signals. However, there has been no evidence that Rho GTPases regulate JNK activation in Wnt/PCP pathway during Xenopus CE movements. Here, we report that Xenopus RhoA (XRhoA), but not Xenopus Cdc42 (XCdc42), is essential for JNK activation downstream of the Wnt/PCP pathway during Xenopus CE movements, and the phenotypic effect of loss of XRhoA function was rescued by Xenopus JNK1 (XeJNK1). In addition, XRhoA rescues the inhibition of CE movements by the DEP domain deletion mutant of Xenopus Dsh (Xdsh-DeltaDEP), which has dominant negative (DN) effects on JNK activation, and the PDZ domain deletion mutant of Xdsh (Xdsh-DeltaPDZ). Moreover, we demonstrate that Xenopus Rho-associated kinase alpha (xROKalpha), which is expressed mainly in mesoderm and ectoderm that undergo extensive cell rearrangements, regulates CE movements without affecting gene expression, and injection of xROKalpha rescued the inhibition of CE movements caused by DN XRhoA. Finally, we show that ROKalpha and JNK synergistically rescued embryos overexpressing DN XRhoA, which exhibit gastrulation defects, although ROKalpha is not required for JNK activation. Together, these data suggest that JNK and ROKalpha function in the noncanonical Wnt/RhoA pathway to regulate Xenopus CE movements.

Animals↗
PubMed2004

Reconstruction of a congenital midpalatal hairy polyp.

Hairy polyps (dermoids or oronasopharyngeal teratomas) are a type of congenital tumour that contain elements of bigerminal origin (ectoderm and mesoderm). We describe a baby who presented with a hairy polyp of the hard palate protruding from the mouth. This was not causing respiratory distress but she had feeding difficulties. She was successfully operated on the age of 5 days, the defect was reconstructed with hairless skin of the mass and she was able to suck after a month.

Female↗
PubMed1997

A chick wingless mutation causes abnormality in maintenance of Fgf8 expression in the wing apical ridge, resulting in loss of the dorsoventral boundary.

We analyzed a Japanese chick wingless mutant (Jwg) to know a molecular mechanism underlying wing development. We observed expression patterns of eleven marker genes to characterize the mutant. Expressions of dorsoventral (DV) and mesenchymal marker genes were intact in nascent Jwg limb buds. However, expression of Fgf8, a marker gene for the apical ectodermal ridge (AER), was delayed and shortly disappeared in the wing regressing AER. Later on, ventral expression of dorsal marker genes of Wnt7a and Lmx1 indicated that the wing bud without the AER became bi-dorsal. In addition, the posterior mesoderm became defective, as deduced from the impaired expression patterns of Sonic hedgehog (Shh), Msx1, and Prx1. We attempted to rescue a wing by implanting Fgf8-expressing cells into the Jwg wing bud. We found that FGF8 can rescue outgrowth of the wing bud by maintaining Shh expression. Thus, the Jwg gene seems to be involved in maintenance of the Fgf8 expression in the wing bud. Further, it is suggested that the AER is required for maintenance of the DV boundary and the polarizing activity of the established wing bud.

Animals↗
PubMed1995

Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis.

Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell-surface receptors and are believed to play a variety of important roles during vertebrate embryogenesis. Bmpr, also known as ALK-3 and Brk-1, encodes a type I transforming growth factor-beta (TGF-beta) family receptor for BMP-2 and BMP-4. Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult mouse tissues. To study the function of Bmpr during mammalian development, we generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutants were recovered from heterozygote matings. Homozygous mutants with morphological defects were first detected at E7.0 and were smaller than normal. Morphological and molecular examination demonstrated that no mesoderm had formed in the mutant embryos. The growth characteristics of homozygous mutant blastocysts cultured in vitro were indistinguishable from those of controls; however, embryonic ectoderm (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5 before morphological abnormalities had become prominent. Teratomas arising from E7.0 mutant embryos contained derivatives from all three germ layers but were smaller and gave rise to fewer mesodermal cell types, such as muscle and cartilage, than controls. These results suggest that signaling through this type I BMP-2/4 receptor is not necessary for preimplantation or for initial postimplantation development but may be essential for the inductive events that lead to the formation of mesoderm during gastrulation and later for the differentiation of a subset of mesodermal cell types.

Alleles↗
PubMed2003

Cell-autonomous involvement of Mab21l1 is essential for lens placode development.

The mab-21 gene was first identified because of its requirement for ray identity specification in Caenorhabditis elegans. It is now known to constitute a family of genes that are highly conserved from vertebrates to invertebrates, and two homologs, Mab21l1 and Mab21l2, have been identified in many species. We describe the generation of Mab21l1-deficient mice with defects in eye and preputial gland formation. The mutant mouse eye has a rudimentary lens resulting from insufficient invagination of the lens placode caused by deficient proliferation. Chimera analyses suggest that the lens placode is affected in a cell-autonomous manner, although Mab21l1 is expressed in both the lens placode and the optic vesicle. The defects in lens placode development correlate with delayed and insufficient expression of Foxe3, which is also required for lens development, while Maf, Sox2, Six3 and PAX6 levels are not significantly affected. Significant reduction of Mab21l1 expression in the optic vesicle and overlying surface ectoderm in Sey homozygotes indicates that Mab21l1 expression in the developing eye is dependent upon the functions of Pax6 gene products. We conclude that Mab21l1 expression dependent on PAX6 is essential for lens placode growth and for formation of the lens vesicle; lack of Mab21l1 expression causes reduced expression of Foxe3 in a cell-autonomous manner.

Animals↗