PubMed Health⌕ Search

Biomedical subjects

H Slavkin

Publications and source records attributed to H Slavkin.

14 recordsLinked to original sources
PubMed1997

Characterization of the fate of midline epithelial cells during the fusion of mandibular prominences in vivo.

The fusion of the mandibular prominences along the midline is achieved with the absence of medial epithelial cells at the fusion site. Failure of fusion of the mandibular prominences results in median cleft of the lower lip and mandible. Cellular and molecular events controlling mandibular fusion were examined during the fusion process in mouse embryogenesis. Cell lineage analyses at the fusion site revealed that epithelial cells migrated to the surface and oral epithelia. DiI-labeled epithelial cells were not observed within the mandibular mesenchyme at any state of fusion. Examination of the midline region did not reveal cells with ultrastructural changes characteristic of apoptotic cell death. An increase in lysosomal enzymes in the midline epithelial cells, which would be correlated with programmed cell death, was not observed. Mice lacking TGF-beta 3 did not have cleft mandible, but had clefting of the secondary palate as a feature of null mutation phenotype. We interpret our comparisons between wild type and homozygous TGF-beta 3 (-/-) mice to suggest that different developmental processes control palatal vs. mandibular fusion. We hypothesize that medical epithelial cells at the fusion site of mandibular prominences migrate to the surface epithelium during the fusion process and neither transdifferentiate into mesenchyme nor express apoptosis.

Animals↗
PubMed1997

TGF-beta isoforms differentially attenuate EGF mitogenicity and receptor activity in fetal lung mesenchymal cells.

To evaluate signaling interactions, combinations of epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) isoforms were applied to primary fetal mouse lung mesenchymal cells isolated at 16 days of gestation. The three isoforms of TGF-beta had similar mitogenic potentials, as assessed by thymidine incorporation (half-maximal effective concentration approximately 2 ng/ml). However, combined exposure to EGF and TGF-beta yielded an isoform-dependent attenuation of EGF-induced mitogenesis. Combinations of 20 ng/ml EGF and 2 ng TGF-beta 1, TGF-beta 2, or TGF-beta 3 resulted in thymidine incorporation values 0.76, 0.74, and 0.86 times that of EGF alone, respectively; attenuation of EGF mitogenicity, interactions between EGF and TGF-beta isoforms, and differences between isoforms were all statistically significant by analysis of variance. Treatment with TGF-beta isoforms significantly reduced EGF-induced receptor angiotensin II substrate phosphorylation. TGF-beta isoform-specific signaling also significantly attenuated EGF-induced phosphorylation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2. These results suggest that isoform-specific TGF-beta signaling modulates the EGF signal transduction pathway upstream of MAP kinase.

Animals↗
PubMed1992

Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III.

Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI type II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The strategy was to use a synthetic degenerative DPP oligonucleotide probe to map this sequence to the long arm of human chromosome 4, 4q13-q21, by using somatic cell hybrids. Our results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. Our data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

Adult↗
PubMed1989

Enamelins and amelogenins share the same amino-terminal sequence.

Previous results from our laboratory indicated that rabbit enamel high molecular weight proteins have the same amino-terminal sequence that amelogenins, thus suggesting the possibility that this domain is shared by both, enamelins and amelogenins. To determine if this is true for other species, enamel proteins and mRNA were extracted from rabbit and hamster developing teeth and analyzed using probes targeted towards the N-terminal sequence of the amelogenins. Our results strongly suggest that both, enamelins and amelogenins share the same amino-terminal amino acid sequence.

Amelogenin↗
PubMed1979

"Proenamel leads to enamel leads to polypeptides": a concept.

Our laboratory is interested in determining the number of enamel protein gene products which characterize the ameloblast phenotype, and to what extent these proteins are degraded as a function of enamel maturation. Many investigators have reported a large number of heterogeneous proteins within the enamel matrix (Eggert, Allen and Burgess, 1973; Weidmann and Eyre, 1971). One explanation for this apparent heterogeneity may be the uncertain age of the analyzed enamel matrix; specimens may have undergone degradative processes associated with enamel maturation. To overcome this difficulty, our laboratory selected 26-day embryonic New Zealand White (NZW) rabbit incisor and molar tooth organs to isolate enamel protein(s). At this developmental stage it is possible to identify newly-secreted enamel matrix proteins.

Amelogenesis↗
PubMedDate not supplied

NIEHS/EPA Workshops. Growth and differentiation factors.

The work group identified a number of research areas where they felt there were significant data gaps where additional research was critical to better under standing of the origins of birth defects and to developing ways for their prevention. These included: 1. Studies designed to determine the role of growth and differentiation factors during pre- and postimplantation stages of development. These investigations could include descriptive studies involving the localization and timing of genes expressed and their products, but must also emphasize and include studies involving the function of these molecules and their interactions in normal and abnormal development. 2. Studies designed to develop and utilize models for investigating normal and abnormal development. These approaches could include in vivo and in vitro techniques, such as creation of genetically defined systems and cell, organ, and whole embryo cultures. These technologies should emphasize ways to study the functions of growth and differentiation factors and the effects of environmental factors. 3. Studies designed to identify environmental agents and their targets in embryonic, extraembryonic, and maternal tissues that may play a role in producing developmental abnormalities through peturbations of growth and differentiation factors. 4. Studies designed to determine cellular and molecular mechanisms for protection and recovery from environmental insults.

Animals↗
PubMedDate not supplied

Presence of dentin phosphoprotein in molars of a patient with dentinogenesis imperfecta type II.

Dentin phosphoprotein (DPP) is the major noncollagenous protein component of the dentin extracellular matrix. This highly acidic phosphorylated protein is solely expressed by the ectomesenchymal-derived odontoblast cells of the tooth organ. Several biochemical studies have suggested diminished levels of, or even the absence of, this protein, which is associated with the human genetic disease dentinogenesis imperfecta (DGI) type II. However, more recent molecular studies have established that the DPP gene locus is not localized to the region of human chromosome 4 (4q13-q21), where several previous linkage analysis studies have mapped DGI types II and III. The purpose of this study was to determine the presence or absence of DPP in the dentition of a patient affected with DGI type II using a sensitive and specific immunodetection method with a polyclonal antibody against mouse DPP. Our results indicate that a 95-kDa protein, immunologically crossreactive with the DPP antibody, was detected within the dentin extracellular matrix of molars isolated from both a proband affected with DGI-II and from an age-matched normal individual. In addition, both DGI-II and normal individuals showed comparable DPP in situ degradation associated with dentin extracellular matrix maturation. These results strongly support the hypothesis that the DPP structural gene does not produce the gene product primarily responsible for the human genetic disease DGI type II.

Adult↗