Transmembrane tyrosine kinases are involved in the control of cell growth and differentiation by ... more Transmembrane tyrosine kinases are involved in the control of cell growth and differentiation by extracellular signals. To enable identification of new receptor tyrosine kinases we developed a method that selectively amplifies segments of receptor genes. The method is based on a combination of polymerase chain reaction (PCR) and hybridization screening and it employs three oligonucleotide primers derived from conserved domains of receptor tyrosine kinases. It yields amplification of receptors' genes and appears to ignore cytoplasmic tyrosine kinases. When applied to RNA from 12.5 days post coitum mouse placenta, this methodology resulted in the detection of several putative or established receptors. Molecular cloning of one of these genes, which is identical to the partially characterized bek gene, identified a transmembrane tyrosine kinase with three immunoglobulin-like domains in the extracellular portion, and a cytoplasmic tyrosine kinase sequence. The isolated cDNA shows rem...
Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilater... more Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilateral ptosis and dysphagia and subsequent limb girdle weakness. The role of the typical intranuclear inclusion in the pathophysiology is unresolved. The aim of this study was to describe the clinical and histopathological features of oculopharyngeal muscular dystrophy (OPMD). We examined this in a Dutch cohort including presymptomatic Ala-expanded-PABPN1 carriers and late symptomatic patients. We performed a prospective, observational study in OPMD patients and adult children of genetically confirmed OPMD patients. The study includes a structured history, a detailed neurological examination, muscle histology and biochemical analysis. Forty patients and 18 adult children participated in this study, among whom were six presymptomatic mutation carriers. One patient died during the study and had given permission to autopsy. In addition to the characteristic OPMD symptoms including ptosis and dysphagia, other symptoms such as limb girdle and axial weakness, and external ophthalmoplegia were frequently observed. Intranuclear aggregates were observed in the biopsies of presymptomatic carriers. Biochemical analysis of the biopsies of the presymptomatic carriers showed no mitochondrial dysfunction. The autopsy showed that muscle weakness correlated with histopathological findings in five different muscles in an individual patient. The main findings of this nationwide study are the presence of intranuclear aggregates before clinical onset and the absence of mitochondrial changes in Ala-expanded-PABPN1 carriers. This indicates that the expression of Ala-expanded-PABPN1 causes the formation of nuclear aggregates before the onset of muscle weakness. Normal results of biochemical analysis in presymptomatic carriers suggest that possible mitochondrial dysfunction occurs later. Furthermore we confirmed that limb girdle weakness occurs frequently in Dutch OPMD patients. This study thus expands the OPMD research towards characterization of presymptomatic carriers.
Variation of flowering time is found in the natural populations of many plant species. The underl... more Variation of flowering time is found in the natural populations of many plant species. The underlying genetic variation, mostly of a quantitative nature, is presumed to reflect adaptations to different environments contributing to reproductive success. Analysis of natural variation for flowering time in Arabidopsis thaliana has identified several quantitative trait loci (QTL), which have yet to be characterized at the molecular level. A major environmental factor that determines flowering time is photoperiod or day length, the length of the light period, which changes across the year differently with geographical latitude. We identified the EDI locus as a QTL partly accounting for the difference in flowering response to the photoperiod between two Arabidopsis accessions: the laboratory strain Landsberg erecta (Ler), originating in Northern Europe, and Cvi, collected in the tropical Cape Verde Islands. Positional cloning of the EDI QTL showed it to be a novel allele of CRY2, encoding...
The continuous growth of the plant embryo is interrupted during the seed maturation processes whi... more The continuous growth of the plant embryo is interrupted during the seed maturation processes which results in a dormant seed. The embryo continues development after germination when it grows into a seedling. The embryo growth phase starts after morphogenesis and ends when the embryo fills the seed sac. Very little is known about the processes regulating this phase. We describe mutants that affect embryo growth in two sequential developmental stages. Firstly, embryo growth arrest is regulated by the FUS3/LEC type genes, as mutations in these genes cause a continuation of growth in immature embryos. Secondly, a later stage of embryo dormancy is regulated by ABI3 and abscisic acid; abi3 and aba1 mutants exhibit premature germination only after embryos mature. Mutations affecting both developmental stages result in an additive phenotype and double mutants are highly viviparous. Embryo growth arrest is regulated by cell division activities in both the embryo and the endosperm, which are...
We have reported the isolation of the Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (A... more We have reported the isolation of the Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (AtSERKl) gene and demonstrated its role during establishment of somatic embryogenesis in culture. The AtSERKl gene is highly ...
Variation of flowering time is found in the natural populations of many plant species. The underl... more Variation of flowering time is found in the natural populations of many plant species. The underlying genetic variation, mostly of a quantitative nature, is presumed to reflect adaptations to different environments contributing to reproductive success. Analysis of natural variation for flowering time in Arabidopsis thaliana has identified several quantitative trait loci (QTL)1, which have yet to be characterized at the molecular level. A major environmental factor that determines flowering time is photoperiod or day length, the length of the light period, which changes across the year differently with geographical latitude2. We identified the EDI locus as a QTL partly accounting for the difference in flowering response to the photoperiod between two Arabidopsis accessions: the laboratory strain Landsberg erecta (Ler), originating in Northern Europe, and Cvi, collected in the tropical Cape Verde Islands3. Positional cloning of the EDI QTL showed it to be a novel allele of CRY2, encod...
Transmembrane tyrosine kinases are involved in the control of cell growth and differentiation by ... more Transmembrane tyrosine kinases are involved in the control of cell growth and differentiation by extracellular signals. To enable identification of new receptor tyrosine kinases we developed a method that selectively amplifies segments of receptor genes. The method is based on a combination of polymerase chain reaction (PCR) and hybridization screening and it employs three oligonucleotide primers derived from conserved domains of receptor tyrosine kinases. It yields amplification of receptors' genes and appears to ignore cytoplasmic tyrosine kinases. When applied to RNA from 12.5 days post coitum mouse placenta, this methodology resulted in the detection of several putative or established receptors. Molecular cloning of one of these genes, which is identical to the partially characterized bek gene, identified a transmembrane tyrosine kinase with three immunoglobulin-like domains in the extracellular portion, and a cytoplasmic tyrosine kinase sequence. The isolated cDNA shows rem...
Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilater... more Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilateral ptosis and dysphagia and subsequent limb girdle weakness. The role of the typical intranuclear inclusion in the pathophysiology is unresolved. The aim of this study was to describe the clinical and histopathological features of oculopharyngeal muscular dystrophy (OPMD). We examined this in a Dutch cohort including presymptomatic Ala-expanded-PABPN1 carriers and late symptomatic patients. We performed a prospective, observational study in OPMD patients and adult children of genetically confirmed OPMD patients. The study includes a structured history, a detailed neurological examination, muscle histology and biochemical analysis. Forty patients and 18 adult children participated in this study, among whom were six presymptomatic mutation carriers. One patient died during the study and had given permission to autopsy. In addition to the characteristic OPMD symptoms including ptosis and dysphagia, other symptoms such as limb girdle and axial weakness, and external ophthalmoplegia were frequently observed. Intranuclear aggregates were observed in the biopsies of presymptomatic carriers. Biochemical analysis of the biopsies of the presymptomatic carriers showed no mitochondrial dysfunction. The autopsy showed that muscle weakness correlated with histopathological findings in five different muscles in an individual patient. The main findings of this nationwide study are the presence of intranuclear aggregates before clinical onset and the absence of mitochondrial changes in Ala-expanded-PABPN1 carriers. This indicates that the expression of Ala-expanded-PABPN1 causes the formation of nuclear aggregates before the onset of muscle weakness. Normal results of biochemical analysis in presymptomatic carriers suggest that possible mitochondrial dysfunction occurs later. Furthermore we confirmed that limb girdle weakness occurs frequently in Dutch OPMD patients. This study thus expands the OPMD research towards characterization of presymptomatic carriers.
Variation of flowering time is found in the natural populations of many plant species. The underl... more Variation of flowering time is found in the natural populations of many plant species. The underlying genetic variation, mostly of a quantitative nature, is presumed to reflect adaptations to different environments contributing to reproductive success. Analysis of natural variation for flowering time in Arabidopsis thaliana has identified several quantitative trait loci (QTL), which have yet to be characterized at the molecular level. A major environmental factor that determines flowering time is photoperiod or day length, the length of the light period, which changes across the year differently with geographical latitude. We identified the EDI locus as a QTL partly accounting for the difference in flowering response to the photoperiod between two Arabidopsis accessions: the laboratory strain Landsberg erecta (Ler), originating in Northern Europe, and Cvi, collected in the tropical Cape Verde Islands. Positional cloning of the EDI QTL showed it to be a novel allele of CRY2, encoding...
The continuous growth of the plant embryo is interrupted during the seed maturation processes whi... more The continuous growth of the plant embryo is interrupted during the seed maturation processes which results in a dormant seed. The embryo continues development after germination when it grows into a seedling. The embryo growth phase starts after morphogenesis and ends when the embryo fills the seed sac. Very little is known about the processes regulating this phase. We describe mutants that affect embryo growth in two sequential developmental stages. Firstly, embryo growth arrest is regulated by the FUS3/LEC type genes, as mutations in these genes cause a continuation of growth in immature embryos. Secondly, a later stage of embryo dormancy is regulated by ABI3 and abscisic acid; abi3 and aba1 mutants exhibit premature germination only after embryos mature. Mutations affecting both developmental stages result in an additive phenotype and double mutants are highly viviparous. Embryo growth arrest is regulated by cell division activities in both the embryo and the endosperm, which are...
We have reported the isolation of the Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (A... more We have reported the isolation of the Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (AtSERKl) gene and demonstrated its role during establishment of somatic embryogenesis in culture. The AtSERKl gene is highly ...
Variation of flowering time is found in the natural populations of many plant species. The underl... more Variation of flowering time is found in the natural populations of many plant species. The underlying genetic variation, mostly of a quantitative nature, is presumed to reflect adaptations to different environments contributing to reproductive success. Analysis of natural variation for flowering time in Arabidopsis thaliana has identified several quantitative trait loci (QTL)1, which have yet to be characterized at the molecular level. A major environmental factor that determines flowering time is photoperiod or day length, the length of the light period, which changes across the year differently with geographical latitude2. We identified the EDI locus as a QTL partly accounting for the difference in flowering response to the photoperiod between two Arabidopsis accessions: the laboratory strain Landsberg erecta (Ler), originating in Northern Europe, and Cvi, collected in the tropical Cape Verde Islands3. Positional cloning of the EDI QTL showed it to be a novel allele of CRY2, encod...
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