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H Reichert

Publications and source records attributed to H Reichert.

At least 37 records · Page 2Linked to original sources
PubMed2001

Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development.

We report loss- and gain-of-function analyses that identify essential roles in development for Drosophila transcription factor AP-2. A mutagenesis screen yielded 16 lethal point mutant alleles of dAP-2. Null mutants die as adults or late pupae with a reduced proboscis, severely shortened legs (approximately 30% of normal length) lacking tarsal joints, and disruptions in the protocerebral central complex, a brain region critical for locomotion. Seven hypomorphic alleles constitute a phenotypic series yielding hemizygous adults with legs ranging from 40-95% of normal length. Hypomorphic alleles show additive effects with respect to leg length and viability; and several heteroallelic lines were established. Heteroallelic adults have moderately penetrant defects that include necrotic leg joints and ectopic growths (sometimes supernumerary antennae) invading medial eye territory. Several dAP-2 alleles with DNA binding domain missense mutations are null in hemizygotes but have dominant negative effects when paired with hypomorphic alleles. In wild-type leg primordia, dAP-2 is restricted to presumptive joints. Ectopic dAP-2 in leg discs can inhibit but not enhance leg elongation indicating that functions of dAP-2 in leg outgrowth are region restricted. In wing discs, ectopic dAP-2 cell autonomously transforms presumptive wing vein epithelium to ectopic sensory bristles, consistent with an instructive role in sensory organ development. These findings reveal multiple functions for dAP-2 during morphogenesis of feeding and locomotor appendages and their neural circuitry, and provide a new paradigm for understanding AP-2 family transcription factors.

Alleles↗
PubMed2000

Observation of five-fold local symmetry in liquid lead.

The local point symmetry of the short-range order in simple monatomic liquids remains a fundamental open question in condensed-matter science. For more than 40 years it has been conjectured that liquids with centrosymmetric interactions may be composed of icosahedral building blocks. But these proposed mobile, randomly orientated structures have remained experimentally inaccessible owing to the unavoidable averaging involved in scattering experiments, which can therefore determine only the isotropic radial distribution function. Here we overcome this limitation by capturing liquid fragments at a solid-liquid interface, and observing the scattering of totally internally reflected (evanescent) X-rays, which are sensitive only to the liquid structure at the interface. Using this method, we observe five-fold local symmetry in liquid lead adjacent to a silicon wall, and obtain an experimental portrait of the icosahedral fragments that are predicted to occur in all close-packed monatomic liquids. By shedding new light on local bond order in disordered structures such as liquids and glasses, these results should lead to a better microscopic understanding of melting, freezing and supercooling.

Journal Article↗
PubMed2000

Quantitative transcript imaging in normal and heat-shocked Drosophila embryos by using high-density oligonucleotide arrays.

Embryonic development in Drosophila is characterized by an early phase during which a cellular blastoderm is formed and gastrulation takes place, and by a later postgastrulation phase in which key morphogenetic processes such as segmentation and organogenesis occur. We have focused on this later phase in embryogenesis with the goal of obtaining a comprehensive analysis of the zygotic gene expression that occurs during development under normal and altered environmental conditions. For this, a functional genomic approach to embryogenesis has been developed that uses high-density oligonucleotide arrays for large-scale detection and quantification of gene expression. These oligonucleotide arrays were used for quantitative transcript imaging of embryonically expressed genes under standard conditions and in response to heat shock. In embryos raised under standard conditions, transcripts were detected for 37% of the 1,519 identified genes represented on the arrays, and highly reproducible quantification of gene expression was achieved in all cases. Analysis of differential gene expression after heat shock revealed substantial expression level changes for known heat-shock genes and identified numerous heat shock-inducible genes. These results demonstrate that high-density oligonucleotide arrays are sensitive, efficient, and quantitative instruments for the analysis of large scale gene expression in Drosophila embryos.

Animals↗
PubMed2000

Expression, regulation and function of the homeobox gene empty spiracles in brain and ventral nerve cord development of Drosophila.

We analyse the role of the empty spiracles (ems) gene in embryonic brain and ventral nerve cord development. ems is differentially expressed in the neurectoderm of the anterior head versus the trunk region of early embryos. A distal enhancer region drives expression in the deutocerebral brain anlage and a proximal enhancer region drives expression in the VNC and tritocerebral brain anlage. Mutant analysis indicates that in the anterior brain ems is necessary for regionalized neurogenesis in the deutocerebral and tritocerebral anlagen. In the posterior brain and VNC ems is necessary for correct axonal pathfinding of specific interneurons. Rescue experiments indicate that the murine Emx2 gene can partially replace the fly ems gene in CNS development.

Animals↗
PubMed2000

Functional expression of a locust visual pigment in transgenic Drosophila melanogaster.

The cDNA encoding a visual pigment of the locust Schistocerca gregaria has been inserted into the germline of the ninaE mutant of Drosophila melanogaster by P-element-mediated transformation. Functional expression has been documented by recording light-regulated electroretinograms in transgenic flies. The spectral properties of the expressed visual pigment were determined with detergent-solubilized material, prepared from the eyecups of the transgenic D. melanogaster. The recombinant locust pigment, as well as the genuine pigment of the fruitfly (Rh1) that served as a control for transformation/expression, showed photoreversibility between the pigment and metapigment forms. The absorptions of the difference spectra identify the locust visual pigment as a short wavelength-absorbing, blue-light-sensitive photoreceptor. The absorption maxima are similar to those recorded on living locust animals. These results show that, although locust visual pigments contain 11-cis retinal as chromophore, the expressed protein is able to adopt 3-hydroxyretinal that is provided by the transgenic fruitflies. The electrophysiological recordings reveal that the locust visual pigment is able to induce phototransduction in the fruitfly. The reported results have two important consequences: On the one hand, the binding site of the locust opsin is apparently able to interact with the 3-hydroxyretinal from Drosophila in a way that the biological signal generated by the photoisomerization of the chromophore can be used by the protein to adopt a physiologically active conformation. On the other hand, despite the relatively large phylogenetic distance between both insect species, the extent of conservation between the protein domains thought to be involved in G-protein activation is striking.

Animals↗
PubMed1999

Neurogenesis in the median domain of the embryonic brain of the grasshopper Schistocerca gregaria.

Embryonic development in the median domain of the brain of the grasshopper Schistocerca gregaria was investigated with immunohistochemical, histological, and intracellular dye injection techniques. The early head midline is divisible into a dorsal median domain and a ventral median domain based on the orientation of cell somata in each region. At 25% of embryogenesis, a single large midline precursor differentiates in the dorsal median domain and produces a lineage of six neuronal progeny before degenerating. No further precursors arise. In addition, the primary commissure pioneers and a pair of lateral neurons differentiate directly from the ectoderm in this region. Lucifer yellow dye injected into the midline precursor stains only this cell and its progeny. Similarly, there is no dye coupling from the primary commissure pioneers to the midline lineage or to neuroblasts of the brain hemispheres. Neurogenesis in the dorsal median domain therefore proceeds separately within each subset of cells, and is not related to development in the brain hemispheres. Beginning at 42% of embryogenesis, the primary commissure pioneers undergo a morphological transformation and concomittantly express the Term-1 antigen. Expression continues throughout embryogenesis and into the adult, where the midline primary commissure pioneer cells are the only ones labeled by Term-1 in the entire brain. The cellular organization of the dorsal median domain therefore remains remarkably conserved throughout embryogenesis, even as the brain undergoes extensive morphological transformation.

Animals↗
PubMed1999

Conserved genetic programs in insect and mammalian brain development.

In recent years it has become evident that the developmental regulatory genes involved in patterning the embryonic body plan are conserved throughout the animal kingdom. Striking examples are the orthodenticle (otd/Otx) gene family and the Hox gene family, both of which act in the specification of anteroposterior polarity along the embryonic body axis. Studies carried out in Drosophila and mouse now demonstrate that these genes are also involved in the formation of the insect and mammalian brain; the otd/Otx genes are involved in rostral brain development and the Hox genes are involved in caudal brain development. These studies also show that the genes of the otd/Otx family can functionally replace each other in cross-phylum rescue experiments and indicate that the genetic mechanisms underlying pattern formation in insect and mammalian brain development are evolutionarily conserved.

Animals↗
PubMed1999

Conserved usage of gap and homeotic genes in patterning the CNS.

The homeotic and cephalic gap genes play central roles in the specification of the anteroposterior animal body axis. Genetic studies carried out in Drosophila and mouse now demonstrate that these genes are also involved in embryonic brain development. The homeotic genes act in posterior brain patterning, and the cephalic gap genes act in anterior brain patterning. Moreover, striking cross-phylum gene replacement experiments show that invertebrate and vertebrate members of the orthodenticle gene family can functionally replace each other. These findings indicate that the genetic mechanisms involved in embryonic brain development are conserved and suggest a common evolutionary origin of the insect and vertebrate brain.

Animals↗
PubMed1998

Developmental rescue of Drosophila cephalic defects by the human Otx genes.

The molecular mechanisms of head development are a central question in vertebrate and invertebrate developmental biology. The anteriorly expressed homeobox gene otd in Drosophila and its homolog Otx in mouse are required for the early development of the most anterior part of the body, suggesting that a fundamental genetic program of cephalic development might be conserved between vertebrates and invertebrates. We have examined this hypothesis by introducing the human Otx genes into flies. By inducing expression of the human Otx homologs with a heat shock promoter, we found that both Otx1 and Otx2 functionally complement the cephalic defects of a fly otd mutant through specific activation and inactivation of downstream genes. Combined with previous morphological studies, these results are consistent with the view that a common molecular ground plan of cephalization was invented before the diversification of the protostome and the deuterostome in the course of metazoan evolution.

Amino Acid Sequence↗
PubMed1998

The wingless gene is required for embryonic brain development in Drosophila.

We have studied the role of the wingless gene in embryonic brain development of Drosophila. wingless is expressed in a large domain in the anlage of the protocerebrum and also transiently in smaller domains in the anlagen of the deutocerebrum and tritocerebrum. Elimination of the wingless gene in null mutants has dramatic effects on the developing protocerebrum; although initially generated, approximately one half of the protocerebrum is deleted in wingless null mutants by apoptotic cell death at late embryonic stages. Using temperature sensitive mutants, a rescue of the mutant phenotype can be achieved by stage-specific expression of functional wingless protein during embryonic stages 9-10. This time period correlates with that of neuroblast specification but preceeds the generation and subsequent loss of protocerebral neurons. Ectopic wingless over-expression in gain-of-function mutants results in dramatically oversized CNS. We conclude that wingless is required for the development of the anterior protocerebral brain region in Drosophila. We propose that an important role of wingless in this part of the developing brain is the determination of neural cell fate.

Animals↗
PubMed1998

Homeotic gene action in embryonic brain development of Drosophila.

Studies in vertebrates show that homeotic genes are involved in axial patterning and in specifying segmental identity of the embryonic hindbrain and spinal cord. To gain further insights into homeotic gene action during CNS development, we here characterize the role of the homeotic genes in embryonic brain development of Drosophila. We first use neuroanatomical techniques to map the entire anteroposterior order of homeotic gene expression in the Drosophila CNS, and demonstrate that this order is virtually identical in the CNS of Drosophila and mammals. We then carry out a genetic analysis of the labial gene in embryonic brain development. Our analysis shows that loss-of-function mutation and ubiquitous overexpression of labial results in ectopic expression of neighboring regulatory genes. Furthermore, this analysis demonstrates that mutational inactivation of labial results in regionalized axonal patterning defects which are due to both cell-autonomous and cell-nonautonomous effects. Thus, in the absence of labial, mutant cells are generated and positioned correctly in the brain, but these cells do not extend axons. Additionally, extending axons of neighboring wild-type neurons stop at the mutant domains or project ectopically, and defective commissural and longitudinal pathways result. Immunocytochemical analysis demonstrates that cells in the mutant domains do not express neuronal markers, indicating a complete lack of neuronal identity. An alternative glial identity is not adopted by these mutant cells. Comparable effects are seen in Deformed mutants but not in other homeotic gene mutants. Our findings demonstrate that the action of the homeotic genes labial and Deformed are required for neuronal differentiation in the developing brain of Drosophila.

Animals↗
PubMed1998

Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development.

Despite the obvious differences in anatomy between invertebrate and vertebrate brains, several genes involved in the development of both brain types belong to the same family and share similarities in expression patterns. Drosophila orthodenticle (otd) and murine Otx genes exemplify this, both in terms of expression patterns and mutant phenotypes. In contrast, sequence comparison of OTD and OTX gene products indicates that homology is restricted to the homeodomain suggesting that protein divergence outside the homeodomain might account for functional differences acquired during brain evolution. In order to gain insight into this possibility, we replaced the murine Otx1 gene with a Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was also observed for the impairments of mesencephalon, eye and lachrymal gland. In contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1-specific function involved in morphogenesis of this structure. Furthermore, otd, like Otx1, was able to cooperate genetically with Otx2 in brain patterning, although with reduced efficiency. These data favour an extended functional conservation between Drosophila otd and murine Otx1 genes and support the idea that conserved genetic functions required in mammalian brain development evolved in a primitive ancestor of both flies and mice.

Animals↗
PubMed1998

Equivalence of the fly orthodenticle gene and the human OTX genes in embryonic brain development of Drosophila.

Members of the orthodenticle gene family are essential for embryonic brain development in animals as diverse as insects and mammals. In Drosophila, mutational inactivation of the orthodenticle gene results in deletions in anterior parts of the embryonic brain and in defects in the ventral nerve cord. In the mouse, targeted elimination of the homologous Otx2 or Otx1 genes causes defects in forebrain and/or midbrain development. To determine the morphogenetic properties and the extent of evolutionary conservation of the orthodenticle gene family in embryonic brain development, genetic rescue experiments were carried out in Drosophila. Ubiquitous overexpression of the orthodenticle gene rescues both the brain defects and the ventral nerve cord defects in orthodenticle mutant embryos; morphology and nervous system-specific gene expression are restored. Two different time windows exist for the rescue of the brain versus the ventral nerve cord. Ubiquitous overexpression of the human OTX1 or OTX2 genes also rescues the brain and ventral nerve cord phenotypes in orthodenticle mutant embryos; in the brain, the efficiency of morphological rescue is lower than that obtained with overexpression of orthodenticle. Overexpression of either orthodenticle or the human OTX gene homologs in the wild-type embryo results in ectopic neural structures. The rescue of highly complex brain structures in Drosophila by either fly or human orthodenticle gene homologs indicates that these genes are interchangeable between vertebrates and invertebrates and provides further evidence for an evolutionarily conserved role of the orthodenticle gene family in brain development.

Animals↗
PubMed1997

Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects.

Ambulatory blood pressure (ABP) monitoring is increasingly used to evaluate the blood pressure of children and adolescents. The upper normal ABP values in the pediatric age group are still unknown, because reference values based on a sufficiently high number of healthy children have not yet been published. In this multicenter trial, we pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm. The study was carried out by seven centers according to a common protocol. The 50th percentile for 24-hour systolic ABP increased moderately with height, from 103 to 113 mm Hg in girls and from 105 to 120 mm Hg in boys. The 50th percentile for diastolic 24-hour means was 66 +/- 1 mm Hg, irrespective of height or gender. Diastolic daytime means were 73 +/- 1 mm Hg, which is remarkably high compared with reference values for casual blood pressure. The mean nocturnal systolic and diastolic ABP (midnight to 6 AM) was 13% +/- 6% and 23% +/- 9% lower compared with the daytime means (8 AM to 8 PM), respectively. This multicenter study provides well-based limits of normal ABP in mid-European children.

Adolescent↗
PubMed1997

Building a brain: developmental insights in insects.

Understanding the cellular, molecular and genetic mechanisms involved in building the brain remains one of the most challenging problems of neurobiology. In this article, we review recent work on the developmental mechanisms that generate the embryonic brain in insects. We compare some of the early developmental events that occur in the insect brain with those that operate during brain development in vertebrates and find that numerous parallels are present at both the cellular and the molecular levels. Thus, the roles of glial cells in prefiguring axon pathways, the function of pioneer neurons in establishing axon pathways, and the formation of a primary axon scaffolding are features of embryonic brain development in both insects and vertebrates. Moreover, at the molecular genetic level homologous regulatory genes control morphogenesis, regionalization and patterning during embryonic brain development in both insects and vertebrates. This indicates that there might be universal mechanisms for brain development, and that knowledge gained from Drosophila and other insects is relevant to our understanding of brain development in other more complex organisms, including man.

Animals↗
PubMed1997

Progressive hydrocephalus in two members of a family with autosomal dominant Noonan phenotype.

We present a family with an autosomal dominant phenotype characterized by pulmonary valve stenosis, craniofacial dysplasia with marked hypertelorism and, as a variable feature, progressive hydrocephalus. This phenotype is manifested in four patients from three subsequent generations of a family, with expression ranging from mild pulmonary stenosis combined with slight but characteristic facial dysmorphism to severe cyanotic pulmonary valve stenosis with multiple malformations lethal in early childhood. We consider this to be an unusual variant of Noonan syndrome.

Adult↗