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At least 1,009 records · Page 56Linked to original sources
PubMed1997

The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation.

We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization. Zic genes were found as a group of genes coding for zinc finger proteins that are expressed in a restricted manner in the adult mouse cerebellum. We showed that the genes are the vertebrate homologues of Drosophila odd-paired, which may play an essential role in parasegmental subdivision and in visceral mesoderm development. The expression of the three Zic genes was first detected at gastrulation in a spatially restricted manner. At neurulation, the expression became restricted to the dorsal neural ectoderm and dorsal paraxial mesoderm. During organogenesis, the three genes were expressed in specific regions of several developing organs, including dorsal areas of the brain, spinal cord, paraxial mesenchyme, and epidermis, the marginal zone of the neural retina and distal regions of the developing limb. For all stages, significant differences in the spatial expression of Zic1, Zic2, and Zic3 were observed. Furthermore, the expression of Zic genes in Pax3, Wnt-1, and Wnt-3a mutant embryos suggested that Zic genes are not primarily regulated by the three genes which were expressed in dorsal areas similar to Zic genes. However, in open brain, a mutant with severe neural tube defects, and in the Wnt-3a mutant mice, the expression of Zic genes was changed. The changed expression pattern in Wnt-3a mutant mice suggests that Zic genes in the neural tube are regulated by the factors from notochord. Our findings suggest that Zic genes are involved in many developmental processes. Furthermore, analysis of gene expression patterns in different mouse mutants indicated that Zic genes may act upstream of many known developmental regulatory genes.

Animals↗
PubMed2002

Depletion of definitive gut endoderm in Sox17-null mutant mice.

In the mouse, the definitive endoderm is derived from the epiblast during gastrulation, and, at the early organogenesis stage, forms the primitive gut tube, which gives rise to the digestive tract, liver, pancreas and associated visceral organs. The transcription factors, Sox17 (a Sry-related HMG box factor) and its upstream factors, Mixer (homeobox factor) and Casanova (a novel Sox factor), have been shown to function as endoderm determinants in Xenopus and zebrafish, respectively. However, whether the mammalian orthologues of these genes are also involved with endoderm formation is not known. We show that Sox17(-/-) mutant embryos are deficient of gut endoderm. The earliest recognisable defect is the reduced occupancy by the definitive endoderm in the posterior and lateral region of the prospective mid- and hindgut of the headfold-stage embryo. The prospective foregut develops properly until the late neural plate stage. Thereafter, elevated levels of apoptosis lead to a reduction in the population of the definitive endoderm in the foregut. In addition, the mid- and hindgut tissues fail to expand. These are accompanied by the replacement of the definitive endoderm in the lateral region of the entire length of the embryonic gut by cells that resemble the visceral endoderm. In the chimeras, although Sox17-null ES cells can contribute unrestrictedly to ectodermal and mesodermal tissues, few of them could colonise the foregut endoderm and they are completely excluded from the mid- and hindgut endoderm. Our findings indicate an important role of Sox17 in endoderm development in the mouse, highlighting the idea that the molecular mechanism for endoderm formation is likely to be conserved among vertebrates.

Animals↗
PubMed2005

Incontinentia pigmenti (IP2): familiar case report with affected men. Literature review.

UNLABELLED: Incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects skin, teeth, eyes and may also have neurological problems. The IP2 name describes the histological characteristics, the incontinence of melanin into the melanocytes cells in the epidermal basal layer and its presence in superficial dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the first time. In a physical exploration she presented sparse and thin hair, eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth have a conic crown and there was also a delayed eruption of other teeth, right eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions and brownish-gray lesions in a lineal pattern. The patient s father had hypopigmented lesions in the posterior regions of both legs. The oral clinical and radiographic exams showed diverse anomalies. Both the patient's and the father's chromosomal studies were normal. DISCUSSION: In the present case we can see that the father has IP2 without supernumeraries X, with the antecedent that his mother had something similar. It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential modulator) gene to a classical one, which was found in some affected men. It is necessary to carry out a molecular study of these patients.

Child, Preschool↗
PubMedDate not supplied

Aplasia cutis congenita in two siblings.

We report on two siblings with aplasia cutis congenita (ACC). This rare congenital malformation is characterized by a local defect of epidermis, dermis, and subcutaneous tissues occurring predominantly on the vertex of the scalp. Patient A (a boy) was born with a parietooccipital 4 x 4 cm scalp defect, that healed under conservative treatment with scar formation within three months. At the age of three years we started with serial excisions of the affected area. In patient B (a girl) two 1.5 x 1.5 cm midline scalp defects were noted at birth. After primary conservative treatment we performed an excision at the age of three years. Both children were born at term following normal pregnancy and delivery. Neither physical nor psychomotor retardation nor any other associated abnormality was found in these cases. Two younger brothers were born without any skin defects or other anomalies. There is no unifying theory on the pathogenesis of ACC. Traumatic, vascular, teratogenic, and genetic factors are discussed as initial steps in etiopathogenesis. In this family the occurrence of ACC in two siblings of either sex, with unaffected parents, may suggest an autosomal recessive mode of transmission. However autosomal dominant inheritance with germline mosaicism in one parent can not be excluded.

Child, Preschool↗
PubMed1975

[The acute phase of leber's optic nerve atrophy (author's transl)].

Optic atrophy and typical visual field defect were found in two brothers some months following a rapid decrease in visual acuity. The optic disc was hyperemic and edematous, furthermore microangiopathy, hemorrhages, and papilloedema were present in the ocular fundus of the third brother some days after an acute loss of central vision. In the present study the pathogenic and differential diagnostic significance of the acute phase of Leber's optic neuropathy is discussed. Considering the fundus changes in the acute phase and the course of the disease, the authors tend to reject the idea of a hereditary systemic disease of the nervous system. The hereditary factors should be searched neither in the nerve tissue nor in the ectodermal system.

Acute Disease↗
PubMed2005

Non-heparan sulfate-binding interactions of endostatin/collagen XVIII in murine development.

Knobloch syndrome is characterized by a congenital generalized eye disease and cranial defect. Pathogenic mutations preferentially lead to a deletion or functional alteration of collagen XVIII's most C-terminal endostatin domain. Endostatin can be released from collagen XVIII and is a potent inhibitor of angiogenesis and tumor growth. We show differential expression of binding partners for endostatin, vascular endothelial growth factor (VEGF), and the collagen XV endostatin homologue in murine embryonal development using a set of alkaline phosphatase fusion proteins. Consistent with the human phenotype, vascular mesenchyme in the developing eye was identified as endostatin's primary target. While endostatin predominantly bound to blood vessels, the VEGF164 affinity probe labeled nonvascular tissues such as forebrain, hindbrain, the optic nerve, and the surface ectoderm of the future cornea. Strikingly increased staining specificity was observed with a non-heparin/heparan sulfate-binding endostatin probe. In contrast, elimination of the heparan sulfate binding site from VEGF led to complete loss of binding. The collagen XV endostatin homologue showed a highly restricted binding pattern. Oligomerization with endogenous endostatin was ruled out by use of collagen XVIII knockout mice. Our data provide strong evidence that collagen XVIII's C-terminal endostatin domain harbors a prominent tissue-binding site and that binding can occur in the absence of heparan sulfates in situ.

Alkaline Phosphatase↗
PubMed2001

Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21.

Developmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.

Abnormalities, Multiple↗
PubMed1995

Reconstruction of aplasia cutis congenita of the scalp by split rib cranioplasty and a free latissimus dorsi muscle flap in a nine month old infant.

We present a case of reconstruction of severe aplasia cutis congenita. Initial treatment with silver sulphadiazine dressings failed and local scalp repair of the defect at age 3 months also failed to provide a stable reconstruction. At age 9 months the infant was experiencing increasing apparent hydrocephalus, shunt infection and brain herniation. The definitive reconstruction was performed with a split rib cranioplasty and a free latissimus dorsi muscle flap. The reconstruction was successful and the infant has a normal head shape and no neurological deficit 12 months postoperatively.

Bone Transplantation↗
PubMed2006

Adams-Oliver syndrome: clinical description of a four-generation family and exclusion of five candidate genes.

We present a Belgian Adams-Oliver syndrome (AOS) family with 10 affected individuals over four generations, of which six were available for this study. Clinical symptoms observed in these patients were very variable as previously reported in other families and included large areas of alopecia on the vertex of the skull and serious limb reduction defects with agenesis of all toes of one foot. To identify the disease-causing gene, we sequenced the MSX1, CART1, P63 (P73L), RUNX2, and HOXD13 genes in this family and nine previously reported families, but no disease-causing mutations were found. Further investigation is ongoing in these families in order to identify the genetic cause of AOS.

DNA Mutational Analysis↗
PubMed2003

Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

Animals↗
PubMed1996

Cellular analysis of limb development in the mouse mutant hypodactyly.

The limb defect in the mouse Hypodactyly (Hd) affects only the distal structures. Heterozygotes (Hd/+) lack all or part of the distal phalanx and the terminal claw of digit on the hindlimbs; mice homozygous (Hd/Hd) for the mutation have just one digit on each of the four limbs. Early limb development in the mutant appears normal and a change in morphology can only be detected later. Limb buds of Hd/+ and Hd/Hd embryos become reduced in width, with Hd/Hd buds becoming very pointed instead of rounded. This change in bud shape is correlated with an increase in cell death anteriorly in Hd/+ hindlimbs and both anteriorly and posteriorly in Hd/Hd fore- and hindlimb buds. The apical ectodermal ridge is very pronounced in pointed Hd/Hd limb buds. Mesenchyme cells from the Hd/Hd mutant in culture show a cell-autonomous change in behaviour and less cartilage differentiates.

Animals↗
PubMed2005

Muscle function and dysfunction in health and disease.

Skeletal muscles of the trunk and limbs developmentally originate from the cells of the dermomyotomal compartment of the somite. A wealth of knowledge has been accumulated with regard to understanding the molecular regulation of embryonic skeletal myogenesis. Myogenic induction is controlled through a complex series of spatiotemporal dependent signaling cascades. Secreted signaling molecules from surrounding structures not only initiate the myogenic program, but also influence proliferation and differentiation decisions. The proper coordination of these molecular events is thus critical for the formation of physiologically functional skeletal muscles. Hereditary congenital skeletal muscle defects arise due to genetics lesions in myogenic specific components. Understanding the mechanistic routes of congenital skeletal muscle disease therefore requires a comprehensive knowledge of the developmental system. Ultimately, the application of this knowledge will improve the diagnostic and therapeutic methodologies for such diseases. The aim of this review is to overview our current understanding of skeletal muscle development and associated human congenital diseases.

Animals↗
PubMed1995

Drosophila midgut morphogenesis requires the function of the segmentation gene odd-paired.

Development of the Drosophila embryonic midgut is dependent on a number of genes, including tinman and bagpipe, which are required for formation of the visceral mesoderm, and the homeotic genes and their targets, which act locally in the visceral mesoderm to direct formation of specific midgut constrictions. Here we report the identification and characterization of another gene, odd-paired (opa), required for normal midgut development. opa, first identified by its pair-rule mutant phenotype in the larval cuticle, encodes a protein containing putative DNA binding domains and other hallmarks of transcriptional regulators. We have positively identified the cloned gene as opa by mapping two null mutations to the open reading frame of the putative opa transcript; these mutations disrupt the open reading frame and generate predicted proteins lacking the DNA binding domain. We demonstrate that opa function is required for formation of the three characteristic midgut constrictions. To understand the mechanisms by which opa contributes to constriction formation, we have analyzed the expression and function of opa throughout midgut development. In the cellular blastoderm, opa is expressed ubiquitously in the ectoderm and mesoderm precursors throughout the presumptive segmented region. As development proceeds, opa expression ceases briefly both in the ectoderm and in the underlying mesodermal cells that later become the visceral mesoderm. We show that in opa mutants the visceral mesoderm is interrupted, evidently due to abnormal expression of bagpipe, a homeodomain gene required for the formation of the visceral mesoderm. At early stages of development in opa mutants, interruptions in the visceral mesoderm are observed at many positions along the anterior-posterior axis. As development proceeds, interruptions are less frequently observed; however, one interruption, coincident with the Antennapedia expression and variability of Ultrabithorax expression in opa mutants. From these observations, we infer that the loss of at least the first and second midgut constrictions in opa mutants is the result of defects first evident in the early stages of visceral mesoderm development.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed2005

Characterization of tiger-tail banding and hair shaft abnormalities in trichothiodystrophy.

BACKGROUND: Tiger tail banding under polarizing light microscopy and hair shaft abnormalities are associated with trichothiodystrophy (TTD), a rare disorder with a wide spectrum of clinical presentations. OBJECTIVE: To characterize the frequency, specificity, and extent of tiger tail banding and hair shaft abnormalities in the spectrum of TTD patients. METHODS: We developed a standardized procedure for microscopic hair examination and studied hairs from 14 TTD and 4 xeroderma pigmentosum (XP)-TTD patients for tiger tail banding and hair shaft abnormalities. For comparison we examined hairs from 173 control donors consisting of 15 normals, 13 XP patients, 11 family members of XP or TTD patients, 101 patients with various cornification disorders, and 33 leukodystrophy patients. Amino acid analysis performed on hair from the TTD and XP-TTD patients showed low sulfur content. RESULTS: Using a rotating microscope stage, all hairs in each TTD sample showed tiger tail banding under polarized light in association with a variety of hair shaft abnormalities (trichoschisis, trichorrhexis nodosa-like defects, surface irregularities, and ribboning). None of the control hairs showed tiger tail banding, and 5 of 173 controls had weathering hair shaft abnormalities. CONCLUSIONS: In patients with clinical features suggestive of TTD, tiger tail banding seen in all hairs with polarizing microscopy, in conjunction with certain hair shaft abnormalities, provides a reliable diagnostic test.

Cystine↗
PubMed1997

Immunochemical characterization of a novel mitochondrially located protein encoded by a nuclear gene within the DFNB8/10 critical region on 21q22.3.

A novel protein encoded by the C210RF2 gene in chromosomal locus 21q22.3 was characterized by immunochemistry. This chromosomal region is known to contain genes for human diseases such as non-syndromic autosomal recessive deafness (DFNB8/10) and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Polyclonal murine antisera were produced against the multivalent peptides deduced from the amino acid sequence of the polypeptide. Immunological reactivity of the obtained antisera was tested with primary cells or established cell lines. On western blotting, the polyclonal sera recognized a single protein product of 25 Kd expressed in cell lines of epithelial and lymphoid origin. Subsequent immunochemistry of several human tissues indicated the ubiquitous expression of the protein. Immunofluorescence studies and co-staining with a mitochondrial-specific dye suggest the subcellular localization of the protein to mitochondria. Mitochondrial localization is also predicted by computer analysis of the polypeptide sequence. As deafness is known to be caused in some instances by defects in mitochondrial function, C210RF2 is a plausible candidate gene for DFNB8/10.

Amino Acid Sequence↗
PubMed2003

Slb/Wnt11 controls hypoblast cell migration and morphogenesis at the onset of zebrafish gastrulation.

During vertebrate gastrulation, highly coordinated cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. In zebrafish, silberblick (slb)/wnt11 regulates normal gastrulation movements by activating a signalling pathway similar to the Frizzled-signalling pathway, which establishes epithelial planar cell polarity (PCP) in Drosophila. However, the cellular mechanisms by which slb/wnt11 functions during zebrafish gastrulation are still unclear. Using high-resolution two-photon confocal imaging followed by computer-assisted reconstruction and motion analysis, we have analysed the movement and morphology of individual cells in three dimensions during the course of gastrulation. We show that in slb-mutant embryos, hypoblast cells within the forming germ ring have slower, less directed migratory movements at the onset of gastrulation. These aberrant cell movements are accompanied by defects in the orientation of cellular processes along the individual movement directions of these cells. We conclude that slb/wnt11-mediated orientation of cellular processes plays a role in facilitating and stabilising movements of hypoblast cells in the germ ring, thereby pointing at a novel function of the slb/wnt11 signalling pathway for the regulation of migratory cell movements at early stages of gastrulation.

Animals↗
PubMed1998

c-kit is expressed in soft tissue sarcoma of neuroectodermic origin and its ligand prevents apoptosis of neoplastic cells.

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF system plays a crucial role in all of these processes and in tumors which derive from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest derivation such as melanocytes) it would appear that an autocrine loop exists between c-kit and SCF, and that the functional block of the c-kit receptors with monoclonal antibodies (MoAbs) results in a significant decrease in cellular proliferation. We studied the expression and role of c-kit and SCF in cell lines of soft tissue sarcoma of neuroectodermic origin, such as Ewing's sarcoma (ES) and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb CD117 PE, c-kit expression was highlighted in all six of the cell lines examined. This receptor was specifically and functionally activated by SCF, as shown by the binding experiments and the intracellular phosphotyrosine and immunoprecipitation studies that were performed. Using reverse transcriptase polymerase chain reaction analysis, five of the six cellular lines expressed the mRNA of SCF. In the medium measured by using an enzyme- linked immunosorbent assay, low concentrations of SCF were found: only the TC32 cellular line produced significantly higher levels (32 pg) than control. In serum-free culture the addition of SCF reduced the percentage of apoptotic cells from 25% to 90% in five out of the six cellular lines. This observation was confirmed by (1) the functional block of c-kit with MoAb: after 7 days of culture more than 30% of the cells were apoptotic (range 31.5% to 100%) in five out of six cell lines and there was also a decrease in the percentage of cells in phase S, and (2) c-kit antisense oligonucleotides: in the cellular lines treated with oligonucleotides (in relation to the untreated lines) there was a notable reduction (P < .001) both in the absolute number of cells and the 3H-thymidine uptake. These results indicate that ES and PNET express c-kit and its ligand SCF and that SCF is capable of protecting the tumor cells against apoptosis. Furthermore, the reverse transcriptase-polymerase chain reaction performed on the biopsies revealed the presence of mRNA both of SCF and c-kit in practically all of the samples studied. Our in vitro data lead us to assume that SCF may also inhibit tumor cell apoptosis in vivo.

Animals↗
PubMed2005

Ocular manifestations of keratitis-ichthyosis-deafness (KID) syndrome.

OBJECTIVE: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported. DESIGN: Retrospective case series. METHODS: Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years. RESULTS: Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient. CONCLUSIONS: KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

Adolescent↗