Biomedical subjects

V Hartenstein

Publications and source records attributed to V Hartenstein.

At least 37 records · Page 2Linked to original sources

PubMed1997

Pattern, time of birth, and morphogenesis of sensillum progenitors in Drosophila.

In this paper we describe the spatiotemporal pattern of sensillum progenitors (SOPs), as well as the way in which these cells segregate from the ectoderm and proliferate. The birthdate of SOPs was determined by applying short heat pulses to embryos carrying the Nintra construct [Struhl et al. (1993), Cell, 74:331-345] which allows the overexpression of the active Notch protein at defined developmental stages and thereby eliminates SOPs which would normally segregate during these stages. Our results show that sensillum progenitors appear in several waves which to some degree respect sensillum modality, as well as dorsoventral sensillum location. The four early SOPs (stage 10) give rise exclusively to multiply innervated sensilla, chordotonal organs, and some multidendritic neurons. The second wave (early stage 11) produces the remaining chordotonal organs, some multidendritic neurons, and the dorsal singly innervated mechanosensilla. The third wave (late stage 11), in a dorsal-to-ventral succession, gives rise to the lateral and ventral singly innervated hair and papilla sensilla. Labeling developing SOPs with specific markers demonstrates that only progenitors of subepidermally located chordotonal organs and multidendritic neurons delaminate, whereas progenitors of external sensilla are born and proliferate within the ectodermal layer.

Animals↗

PubMed1997

Control of early neurogenesis of the Drosophila brain by the head gap genes tll, otd, ems, and btd.

The progenitors of the Drosophila central nervous system (CNS), called neuroblasts, segregate from the neurectoderm of the early embryo in a stereotyped pattern. The neuroblasts that give rise to the brain segregate from the procephalic neurectoderm and form three neuromeres, called protocerebrum, deuterocerebrum, and tritocerebrum. The expression of the proneural genes of the achaete-scute complex (AS-C) is required for neurectodermal cells to acquire the competency to form neuroblasts. We show here that the expression of the proneural gene lethal of scute (l'sc) is required for the development of the majority of the procephalic neuroblasts. l'sc expression in the procephalic neurectoderm is controlled by the head gap genes tailless (tll), orthodenticle (otd), buttonhead (btd), and empty spiracles (ems), which are expressed in partially overlapping domains of the head neurectoderm. Loss of function of a given head gap gene results in the absence of l'sc expression in its domain, followed by the absence of neuroblasts that would normally segregate from this domain. Loss of tll function results in the absence of all protocerebral neuroblasts, otd functions in a domain that includes a large part of the protocerebrum and a smaller part of the adjacent deuterocerebrum. Both ems and btd are required in partially overlapping subsets of neuroblasts of the deuterocerebrum and tritocerebrum.

Animals↗

PubMed1997

Development of the insect stomatogastric nervous system.

The stomatogastric nervous system (SNS) forms a network of peripheral ganglia associated with the insect gut. The SNS originates from a neuroepithelial placode which dissolves into a population of migrating neural precursors. The formation of the SNS presents many parallels to the development of the vertebrate peripheral nervous system. Recent studies have started to provide answers for pertinent questions in SNS development, in particular, how the SNS placode is specified, how SNS precursors are released in a reproducible pattern from this placode and how different cell types in the SNS are determined.

Animals↗

PubMed1997

InsP3 receptor is essential for growth and differentiation but not for vision in Drosophila.

Phospholipase C (PLC) is the focal point for two major signal transduction pathways: one initiated by G protein-coupled receptors and the other by tyrosine kinase receptors. Active PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into the two second messengers inositol 1,4,5-trisphosphate (InsP3) and diacyl glycerol (DAG). DAG activates protein kinase C, and InsP3 mobilizes calcium from intracellular stores via the InsP3 receptor. Changes in [Ca2+]i regulate the function of a wide range of target proteins, including ion channels, kinases, phosphatases, proteases, and transcription factors (Berridge, 1993). In the mouse, there are three InsP3R genes, and type 1 InsP3R mutants display ataxia and epileptic seizures (Matsumoto et al., 1996). In Drosophila, only one InsP3 receptor (InsP3R) gene is known, and it is expressed ubiquitously throughout development (Hasan and Rosbash, 1992; Yoshikawa et al., 1992; Raghu and Hasan, 1995). Here, we characterize Drosophila InsP3R mutants and demonstrate that the InsP3R is essential for embryonic and larval development. Interestingly, maternal InsP3R mRNA is sufficient for progression through the embryonic stages, but larval organs show asynchronous and defective cell divisions, and imaginal discs arrest early and fail to differentiate. We also generated adult mosaic animals and demonstrate that phototransduction, a model PLC pathway thought to require InsP3R, does not require InsP3R for signaling.

Animals↗

PubMed1997

Complex regulatory region mediating tailless expression in early embryonic patterning and brain development.

tailless encodes a transcription factor expressed in multiple domains in the developing embryo. Early and transient expression at the posterior pole is required to establish a domain from which the eighth abdominal segment, telson and posterior gut arise. Just a few nuclear cycles later, a brain-specific domain is initiated at the anterior; expression in this domain is maintained with complex modulations throughout embryogenesis. Expression of tailless in this domain is required to establish the most anterior region of the brain. To understand the function and regulation of these different domains of expression, we provide a detailed description of tailless expression in brain neuroblasts and show that this expression is not detectably regulated by the head gap genes buttonhead or orthodenticle, by the proneural gene lethal of scute or by tailless itself. We show that approximately 6 kb of sequenced upstream regulatory DNA can drive lacZ expression in a pattern that mimics the full tailless embryonic expression pattern. Within this sequence we identify multiple modules responsible for different aspects of the tailless pattern. In addition to identifying additional torso response elements that mediate early blastoderm polar expression, we show that the complex brain expression pattern is driven by a combination of modules; thus expression at a low level throughout the brain and at a high level in the dorsal medial portion of the brain and in the optic lobe, as well as neuroblast-specific repression are mediated by different DNA regions.

Animals↗

PubMed1996

Early neurogenesis of the Drosophila brain.

We have studied the formation of the neuroblasts of the Drosophila brain which segregate from the procephalic neurectoderm. The expression domains of the segment polarity gene engrailed (en) allow one to subdivide the procephalic neuroectoderm into tritocerebral, deuterocerebral, and protocerebral neuromeres. Based upon the expression pattern of the proneural gene lethal of scute (l'sc), as well as the pattern of brain neuroblast segregation, the protocerebral and deuterocerebral neuromeres can be further subdivided into a central, anterior, and posterior domain. A total of 75-80 neuroblasts segregate in a stereotyped pattern from the procephalic neurectoderm of each side during stages 9-11. With respect to their position and the expression of the markers asense (ase) and seven-up (svp), 23 small groups of one to five neuroblasts each were identified. The first eight groups (Pc1-4, Dc1-3, Dp1), collectively called SI/II neuroblasts in analogy to the subpopulation of ventral neuroblasts which appear at the same stage), arise from the central domain of the protocerebral and deuterocerebral neurectoderm, respectively. Later groups form anteriorly and posteriorly from the earlier ones, leading to a centrifugal growth of the procephalic neuroblast population. SIII neuroblasts (Pa1-4, Pp1-2, Dp2) arise during stage 10, SIV neuroblasts (Pa5-6, Pp3-4, Da1, T1-2) during early stage 11, and SV neuroblasts (Pp5, Pdm) during late stage 11 and early stage 12. The dorsomedial domain of the procephalic neurectoderm represents a special case. Unlike other procephalic neuroblasts which delaminate from the surface ectoderm as individual cells, cells of the dorsomedial protocerebral domain are internalized during stage 12 as large, coherent clusters by a movement which can be best characterized as a combination of mass-delamination and invagination.

Animals↗

PubMed1996

shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia.

Adhesion molecules of the cadherin superfamily have an important role during vertebrate development. The DE-cadherin homolog DE-cadherin is the first classic cadherin isolated from invertebrates. We report here that DE-cadherin is encoded by the shotgun (shg) gene. shg is expressed in most embryonic epithelia and decreases in cells that undergo epithelial-mesenchymal transitions like the mesoderm or neural precursors. Removal of both maternal and zygotic shg function leads to severe defects in all epithelia expressing shg, suggesting that DE-cadherin, similar to vertebrate classic cadherins, has a crucial role for the formation and/or maintenance of epithelial tissues. Interestingly, the analysis of different shg alleles indicates that the requirement for shg in a given epithelium depends on the degree of its morphogenetic activity. Only epithelia involved in extensive morphogenetic movements require zygotic shg function in addition to maternal expression. In support of this view we find that suppression of morphogenetic movements rescues the zygotic shg phenotype. We find that in zygotic shg nulls the level of Dalpha-catenin and Armadillo at adherens junctions is dramatically reduced, surprisingly also in epithelia that differentiate normally and possess a zonula adherens.

Animals↗

PubMed1996

Proneural and neurogenic genes control specification and Morphogenesis of stomatogastric nerve cell precursors in Drosophila.

The stomatogastric nervous system (SNS) of the Drosophila embryo develops from a placode which appears in the stomodeam epithelium. Most cells of this placode invaginate as three pouches (the iSNSPs) into the interior of the embryo. After separating from the stomodeum, the SNS pouches transiently form epithelial vesicles and eventually dissociate into solid clusters of cells which migrate on the foregut epithelium and differentiate into the neurons of the SNS. Prior and during iSNSP invagination, two small subpopulations of SNSPs (dSNSPs and tSNSPs) delaminate as individual cells from the SNS placode (Hartenstein et al., 1994). The results presented in this paper show that the neurogenic and proneural genes are expressed and required during all phases of SNS development to control the number, pattern, and structural characteristics of the SNSP subpopulations. First, loss-of-function mutations of the proneural and gain-of-function mutations of the neurogenic genes result in the absence or reduction of delaminating SNSPs; loss of function of neurogenic genes leads to the overproduction of d/tSNSPs and a loss of iSNSPs. Second, both proneural and neurogenic genes are involved in the invagination and dissociation of iSNSPs. Reduction of neurogenic gene function leads to a premature dissociation of iSNSPs; gain of neurogenic gene function blocks invagination and dissociation of these cells. Since all iSNSPs form a homogenous population with regard to their differentiative fate as SNS neurons, these results indicate that lateral inhibition is not a necessary aspect of the developmental process controlled by neurogenic and proneural gene function.

Animals↗

PubMed1995

A graphic digital database of Drosophila embryogenesis.

Modern studies of the genetic control of development have increased the need for an accurate and comprehensive storage and display of gene expression data. This can be achieved in the form of an electronic graphic database of development. Here, we introduce the first steps towards a database of Drosophila embryogenesis. For each morphologically defined stage, a complete series of histological and/or optical sections are generated (optical sections are generated by laser confocal microscopy). Digitized sections are imported into a drawing program where they serve as templates to define the contours of organs and the position of individual cells. From these data, surface and point cloud models of all developmental stages are generated. Gene expression data can be entered by translating the expression domain of a given gene into the three-dimensional coordinate system of the database.

Analog-Digital Conversion↗

PubMed1995

The role of yan in mediating the choice between cell division and differentiation.

An allele of the yan locus was isolated as an enhancer of the Ellipse mutation of the Drosophila epidermal growth factor receptor (Egfr) gene. This yan allele is an embryonic lethal and also fails to complement the lethality of anterior open (aop) mutations. Phenotypic and complementation analysis revealed that aop is allelic to yan and genetically the lethal alleles act as null mutations for the yan gene. Analysis of the lethal alleles in the embryo and in mitotic clones showed that loss of yan function causes cells to overproliferate in the dorsal neuroectoderm of the embryo and in the developing eye disc. Our studies suggest that the role of yan is defined by the developmental context of the cells in which it functions. An important role of this gene is in allowing a cell to choose between cell division and differentiation. The relationship of the Egfr and Notch pathways to this developmental role of yan is discussed.

Alleles↗

PubMed1995

Neurogenic and proneural genes control cell fate specification in the Drosophila endoderm.

The Drosophila endoderm segregates into three non-neural cell types, the principle midgut epithelial cells, the adult midgut precursors, and the interstitial cell precursors, early in development. We show that this process occurs in the absence of mesoderm and requires proneural and neurogenic genes. In neurogenic mutants the principle midgut epithelial cells are missing and the other two cell types develop in great excess. Consequently, the midgut epithelium does not form. In achaete-scute complex and daughterless mutants the interstitial cell precursors do not develop and the number of adult midgut precursors is strongly reduced. Development of the principle midgut epithelial cells and formation of the midgut epithelium is restored in neurogenic proneural double mutants. The neurogenic/proneural genes are, in contrast to the neuroectoderm, not expressed in small clusters of cells but initially homogeneously in the endoderm suggesting that no prepattern exists which determines the position of the segregating cells. Hence, the segregation pattern solely depends on neurogenic/proneural gene interaction. Proneural genes are required but not sufficient to determine specific cell fates because they are required for cell type specification in both ectoderm and endoderm. Our data also suggest that the neurogenic/proneural genes are involved in the choice between epithelial versus mesenchymal cell morphologies.

Animals↗

PubMed1995

Homeobox genes and connective tissue patterning.

In vertebrates, limb tendons are derived from cells that migrate from the lateral plate mesoderm during early development. While some of the developmental steps leading to the formation of these tissues are known, little is known about the molecular mechanisms controlling them. We have identified two murine homeobox-containing genes, Six 1 and Six 2, which are expressed in a complementary fashion during the development of limb tendons. Transcripts for both genes are found in different sets of phalangeal tendons. Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes.

Amino Acid Sequence↗

PubMed1994

Embryonic development of the stomatogastric nervous system in Drosophila.

Using several cell-specific markers, the pattern of proliferation, morphogenesis, and neuronal differentiation of the Drosophila larval stomatogastric nervous system (SNS) was analyzed. In the late embryo, four SNS ganglia (frontal ganglion, hypocerebral ganglion, paraesophageal ganglion, ventricular ganglion) can be distinguished. In the early embryo, the precursor cells of the SNS (SNSPs), being an integral part of the anlage of the esophagus, undergo four synchronous rounds of division. Subsequently, SNSPs segregate from the esophageal epithelium in a complex and stereotyped pattern. The majority of SNSPs invaginate and transiently form three (rostral, intermediate, caudal) pouches that, after separating from the esophagus, become epithelial vesicles. At later stages, these SNSPs gradually lose their epithelial phenotype. Starting at the anterior-dorsal tip of each vesicle, SNSPs dissociate from one another and migrate to the various locations where they differentiate as neurons. Cells of the rostral and intermediate vesicle contribute to the frontal ganglion; the hypocerebral ganglion develops from the intermediate vesicle, the paraesophageal ganglion from the rostral vesicle, and the ventricular ganglion from the caudal vesicle. In addition to the invaginating SNSPs, several distinct groups of SNSPs delaminate as individual cells from the esophageal epithelium. Three clusters of SNSPs delaminate from a region anterior to the rostral pouch; a single SNSP delaminates from the tip of each pouch. All delaminating SNSPs contribute to the frontal ganglion. A significant number of SNSPs undergo cell death. In the late embryo, the stomatogastric ganglia are interconnected by the recurrent nerve and esophageal nerves. The frontal ganglion projects to the brain via the frontal connectives. Both recurrent nerve and frontal connectives are pioneered by small subpopulations of early differentiating stomatogastric neurons that most likely derive from among the dSNSPs and iSNSPs.

Animals↗

PubMed1994

The development of cellular junctions in the Drosophila embryo.

The pattern and development of cellular junctions in the different tissues of the Drosophila embryo from the blastoderm stage until hatching were analyzed. The cellular junctions found include: gap junctions, two types of septate junctions, and several types of cell-cell and cell-substrate adherens junctions. During early and mid embryogenesis (stages 4 to 13) only spot adherens junctions, gap junctions, and zonulae adherentes prevail. Scattered spot adherens junctions are already formed at the blastoderm stage. During and shortly after gastrulation, spot adherens junctions become concentrated at the apical pole and fuse into continuous zonulae adherentes in the posterior endoderm and the ectoderm. In addition to the zonulae adherentes, ectodermally derived epithelia possess scattered gap junctions and form pleated septate junctions and hemiadherens junctions during late embryogenesis (stages 14 to 17). Mesenchymal tissues (i.e., all nonepithelial tissues of the embryo, including the neural primordium and, transiently, the mesoderm and endoderm) possess both spot adherens junctions and gap junctions at a low frequency. Initially, the midgut epithelium does not establish a junctional complex and possess only gap junctions and spot adherens junctions. Only late in development does a circumferential smooth septate junction develop; zonulae adherentes are missing. The various derivatives of the mesoderm express spot adherens junctions, hemiadherens junctions, and gap junctions, but never zonulae adherentes or septate junctions. After organogenesis, several different types of tissue-specific adherens junctions are formed, among them connecting hemiadherens junctions (between gut epithelium and visceral muscle and early during the formation of the muscle tendon junction), muscle tendon junctions (between somatic muscle and tendon cells), fasciae adherentes (between the cells of both the visceral muscle and the dorsal vessel), and autocellular nephrocyte junctions (in nephrocytes). Interesting exceptions to the general pattern of junctional development are provided by the outer epithelial layer of the proventriculus and the Malpighian tubules. Both tissues develop as typical ectodermal epithelia and possess zonulae adherentes. During late embryogenesis, both epithelia lose the zonulae adherentes and form smooth rather than pleated septate junctions, thereby expressing a junctional complex similar to that of the endodermally derived midgut epithelium.

Animals↗

PubMed1994

Delamination and division in the Drosophila neurectoderm: spatiotemporal pattern, cytoskeletal dynamics, and common control by neurogenic and segment polarity genes.

Cytoskeletal changes occurring during the delamination of precursors of the peripheral (microchaete precursors in the pupal notum) and central nervous system (embryonic SI neuroblasts) were studied. The pattern of cell division in the ventral neurectoderm (VN) of wild-type embryos was analyzed using BrdU incorporation and correlated to the pattern of neuroblast delamination. Finally, defects in the pattern of proliferation of the VN and neuroblast delamination which occur in Notch and wingless mutant embryos were described. The results indicate that the patterns of delamination and mitosis are closely correlated: delamination occurs either immediately after a cell has divided (in case of microchaete precursors) or shortly before the division (in case of the neuroblasts). In addition, cytoskeletal changes similar to those occurring during mitosis can be seen in delaminating neuronal precursors. Thus, during both mitosis and delamination, the discrete apicobasally oriented microfilament-tubulin bundles break down. Microfilaments form a dense, diffuse cortical layer surrounding the entire cell body. Microtubules are concentrated at the apically located centrosome. The relationship between mitosis and delamination is supported by the finding that the neurogenic gene Notch and segment polarity gene wingless (wg) affect both proliferation and delamination in the ventral neurectoderm. Thus, in embryos expressing the trunkated cytoplasmic domain of the neurogenic gene Notch under heat-shock control (Struhl et al., 1993), all ventral neurectodermal cells go into mitosis prematurely, followed by the absence of neuroblast delamination. In wg loss-of-function mutants, mitosis in the VN is irregular and generally postponed, accompanied by irregularities in the timing of neuroblast delamination in general and the absence of a subset of neuroblasts.

Actin Cytoskeleton↗

PubMed1994

The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system.

The transformation of an unpatterned epithelium into a patterned one is a fundamental issue in morphogenesis. This transformation occurs in a dramatic fashion in the developing eye imaginal disc, the primordium of the Drosophila compound eye. Molecular and developmental analyses reveals that the sine oculis (so) locus encodes a homeodomain-containing protein that is expressed and required in the unpatterned epithelium prior to morphogenesis. In mutants, cells undergo apoptosis. These findings argue that so plays an essential role in controlling the initial events of pattern formation in the eye disc. So is also expressed and required for the development of the rest of the fly visual system, including the optic lobes (i.e., those regions of the brain that process visual information). So is expressed in the optic lobe primordium prior to its invagination from the embryonic ectoderm; in so mutants, the optic lobe primordium fails to invaginate.

Alleles↗

PubMed1994

Epithelium formation in the Drosophila midgut depends on the interaction of endoderm and mesoderm.

The reorganization of mesenchymal cells into an epithelial sheet is a widely used morphogenetic process in metazoans. An example of such a process is the formation of the Drosophila larval midgut epithelium that develops through a mesenchymal-epithelial transition from endodermal midgut precursors. We have studied this process in wild type and a number of mutants that show defects in midgut epithelium formation. Our results indicate that the visceral mesoderm serves as a basal substratum to which endodermal cells have to establish direct contact in order to form an epithelium. Furthermore, we have analyzed the midgut phenotype of embryos mutant for the gene shotgun, and the results suggest that shotgun directs adhesion between midgut epithelial cells, which is independent from the adhesion between endoderm and visceral mesoderm.

Animals↗

PubMed1994

Embryonic origin of hemocytes and their relationship to cell death in Drosophila.

We have studied the embryonic development of Drosophila hemocytes and their conversion into macrophages. Hemocytes derive exclusively from the mesoderm of the head and disperse along several invariant migratory paths throughout the embryo. The origin of hemocytes from the head mesoderm is further supported by the finding that in Bicaudal D, a mutation that lacks all head structures, and in twist snail double mutants, where no mesoderm develops, hemocytes do not form. All embryonic hemocytes behave like a homogenous population with respect to their potential for phagocytosis. Thus, in the wild type, about 80-90% of hemocytes become macrophages during late development. In mutations with an increased amount of cell death (knirps; stardust; fork head), this figure approaches 100%. In contrast, in these mutations, the absolute number of hemocytes does not differ from that in wild type, indicating that cell death does not 'induce' the formation of hemocytes. Finally, we show that, in the Drosophila embryo, apoptosis can occur independently of macrophages, since mutations lacking macrophages (Bicaudal D; twist snail double mutants; torso4021) show abundant cell death.

Animals↗