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M Bate

Publications and source records attributed to M Bate.

At least 37 records · Page 2Linked to original sources
PubMed1997

Specific muscle identities are regulated by Krüppel during Drosophila embryogenesis.

During Drosophila embryogenesis, mesodermal cells are recruited to form a complex pattern of larval muscles. The formation of the pattern is initiated by the segregation of a special class of founder myoblasts. Single founders fuse with neighbouring nonfounder myoblasts to form the precursors of individual muscles. Founders and the muscles that they give rise to have specific patterns of gene expression and it has been suggested that it is the expression of these founder cell genes that determines individual muscle attributes such as size, shape, insertion sites and innervation. We find that the segmentation gene Krüppel is expressed in a subset of founders and muscles, regulates specific patterns of gene expression in these cells and is required for the acquisition of proper muscle identity. We show that gain and loss of Krüppel expression in sibling founder cells is sufficient to switch these cells, and the muscles that they give rise to, between alternative cell fates.

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PubMed1997

Segregation of myogenic lineages in Drosophila requires numb.

Terminal divisions of myogenic lineages in the Drosophila embryo generate sibling myoblasts that found larval muscles or form precursors of adult muscles. Alternative fates adopted by sibling myoblasts are associated with distinct patterns of gene expression. Genes expressed in the progenitor cell are maintained in one sibling and repressed in the other. These differences depend on an asymmetric segregation of Numb between sibling cells. In numb mutants, muscle fates associated with repression are duplicated and alternative muscles are lost. If numb is overexpressed the reverse transformation occurs. Numb acts to block Notch-mediated repression of genes expressed in muscle progenitor cells. Thus asymmetric cell divisions are essential determinants of muscle fates during myogenesis in Drosophila

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PubMed1996

twist: a myogenic switch in Drosophila.

Somatic muscle is derived from a subset of embryonic mesoderm. In Drosophila, Twist (Twi), a basic helix-loop-helix transcription factor, is a candidate regulator of mesodermal differentiation and myogenesis. Altering amounts of Twist after gastrulation revealed that high levels of Twist are required for somatic myogenesis and block the formation of other mesodermal derivatives. Expression of twist in the ectoderm drives these cells into myogenesis. Thus, after an initial role in gastrulation, twist regulates mesodermal differentiation and propels a specific subset of mesodermal cells into somatic myogenesis. Vertebrate homologs of twist may also participate in the subdivision of mesoderm.

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PubMed1996

Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones.

We describe the extent to which presynaptic structures at the embryonic neuromuscular junction of Drosophila can form in mutants where development of postsynaptic somatic muscles is affected. Although twist mutant embryos lack mesoderm, motor axons still grow out of the CNS and form morphologically normal presynaptic active zones, independent of their target cells. In myoblast city mutant embryos, myoblasts do not fuse but form fully differentiated mononucleate muscles, which make functional neuromuscular synapses with correctly localized presynaptic active zones. Myoblasts also fail to fuse but still attract appropriate innervation in mef2 mutant embryos. However, these myoblasts fail to differentiate into muscles and presynaptic active zones fail to localize at neuromuscular contacts. Thus, the process of synapse formation can be genetically separated from the process of target recognition, revealing that localization of presynaptic active zones requires mef2-dependent muscle differentiation.

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PubMed1996

The drosophila neuromuscular junction: a model system for studying synaptic development and function.

The Drosophila neuromuscular junction has attracted widespread attention as an excellent model system for studying the cellular and molecular mechanisms of synaptic development and neurotransmission. In Drosophila the advantages of invertebrate small systems, where individual cells can be examined with single-cell resolution, are combined with the powerful techniques of patch-clamp analysis and molecular genetics. In this review we examine myogenesis and motoneuron development, the problems of axon outgrowth and target selection, the differentiation of the synapse, and the mechanisms of both synaptic function and plasticity in this model genetic system.

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PubMed1995

Lethal of scute, a proneural gene, participates in the specification of muscle progenitors during Drosophila embryogenesis.

The mechanisms that underlie the segregation of muscle founder cells in the Drosophila embryo are undefined. We show that the proneural gene lethal of scute (l'sc) is expressed in clusters of cells in the somatic mesoderm, from which individual muscle progenitors are singled out by progressive restriction of l'sc expression. Coexpression of l'sc and S59 (a putative muscle identity gene) in a subset of muscle progenitors shows that muscle founders are produced by division of muscle progenitors. In neurogenic mutant embryos the restriction of l'sc expression fails and all cells in a cluster coexpress l'sc and S59. Loss-of-function and overexpression phenotypes indicate a role for l'sc in the segregation of muscle progenitors and the formation of the muscle pattern.

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PubMed1995

wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis.

The final pattern of the Drosophila larval body wall muscles depends critically on the prior segregation of muscle founder cells. We would like to understand the underlying molecular mechanisms which ensure the precise allocation and placement of these muscle founder cells. We have begun our analysis by examining the role of the segment polarity genes, known to be involved in the patterning of the ectoderm. Mutations in only one member of this class, wingless (wg), lead to the complete loss of a subset of muscle founder cells characterised by the expression of S59. Using the GAL4-targetted expression system, we find that Wingless, a secreted glycoprotein and well characterized signalling molecule, acts directly on the mesoderm to ensure the formation of S59-expressing founder cells. Moreover, we present evidence that Wg can signal across germ layers and that, in the wild-type embryo, Wg from the ectoderm could constitute an inductive signal for the initiation of the development of a subset of somatic muscles.

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PubMed1995

Anterior-posterior subdivision and the diversification of the mesoderm in Drosophila.

We have used a novel cell marker, in which the twist promoter directs the synthesis of the cell surface protein CD2 (twi-CD2) to examine the development of the mesoderm in the Drosophila embryo after gastrulation and to locate the progenitor cell populations for different mesodermal derivatives. We find that the early mesoderm in each segment is divided into a more anterior region with relatively low levels of twist and twi-CD2 expression and a more posterior region where twist and twi-CD2 expression are high. This subdivision coincides with regional assignments of cells to form different progenitors: dorsal anterior cells invaginate to form an internal layer from which the visceral mesoderm is derived. Ventral anterior cells form progenitors of mesodermal glial cells. Dorsal posterior cells form heart. Ventral and dorsal posterior cells form somatic muscles. We conclude that the metamerically repeated anterior-posterior subdivision of the mesoderm is an essential element in laying out the pattern of mesodermal progenitor cells and in distinguishing between an internal cell layer which will give rise to the progenitors of visceral muscles and an external layer which will generate the somatic muscles and the heart.

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PubMed1995

Mutations in a novel gene, myoblast city, provide evidence in support of the founder cell hypothesis for Drosophila muscle development.

We have used mutations in the newly identified gene myoblast city to investigate the founder cell hypothesis of muscle development in Drosophila melanogaster. In embryos mutant for myoblast city the fusion of myoblasts into multinucleate muscles is virtually abolished. Nevertheless, a subset of the myoblasts develop specific muscle-like characteristics, including gene expression appropriate to particular muscles, migration to the appropriate part of the segment, correct position and orientation, and contact by motor neurons. We suggest that this subset of myoblasts represents the proposed muscle founder cells and we draw an analogy between these founder cells and the muscle pioneers described for grasshopper muscle development.

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PubMed1995

Innervation is essential for the development and differentiation of a sex-specific adult muscle in Drosophila melanogaster.

The adult abdominal muscles in Drosophila are generated de novo during metamorphosis and form a simple and characteristic pattern. Throughout adult abdominal development there is a close association between nerves and myoblasts. However, the role of innervation in adult myogenesis is unclear. In males there is an additional muscle, which is unique to abdominal segment 5 (A5). This male specific muscle forms from the same pool of myoblasts as other dorsal muscles in A5 but develops several distinctive characteristics. Previous work indicates the genotype of the innervation of this male specific muscle may play a crucial role in its proper development, although the part played by innervation in the development of other muscles is unknown. Here we test directly the function of innervation in adult myogenesis in general and for the development and differentiation of the male specific muscle in particular. After denervation at the onset of metamorphosis, muscle growth is impaired although the overall muscle pattern continues to develop. Uniquely, the male specific muscle fails to form. Our results indicate that there is an essential role for innervation during the period of metamorphosis for the formation of a full complement of abdominal muscles and for muscle growth. Furthermore, innervation is absolutely required for the formation of the male specific muscle and the development of its special characteristics.

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PubMed1993

The differentiation between neuroglia and connective tissue sheath in insect ganglia revisited: the neural lamella and perineurial sheath cells are absent in a mesodermless mutant of Drosophila.

Two morphogenetic mutations, twist and Delta, that affect the embryonic development of Drosophila in known ways were used to examine the derivation and function of the outer layers of the central nervous system (CNS). Both the extracellular neural lamella, which ensheaths the CNS, and its source, the underlying perineurial sheath cell layer, fail to develop in Drosophila embryos that are homozygous for a loss of function mutation in the twist gene, and which thus lack mesodermal derivatives. The cell layer immediately below the perineurial sheath cells, here termed barrier glial cells, constitute the ion permeability barrier in wild-type embryos. They are present in twist mutant embryos, appear to be normal at the ultrastructural level, and function as a blood-brain ion barrier. The apparent derivation of perineurial sheath cells from mesodermal precursors distinguishes them from neurons, glia and other nonneural components of the CNS, such as tracheae, all of which are of ectodermal origin. We confirm Scharrer's interpretation of the relationship between the perineurium and underlying neuroglia. In embryos homozygous for the neurogenic mutant Delta, an embryonic lethal in which excess ventral blastoderm gives rise to neuroblasts, the CNS forms as an amorphous cell mass, with discontinuous perineurial sheath and barrier glial cell layers. We propose that the cell mass is permeable to lanthanum ions and fails to form a blood-brain barrier because volume growth prevents the formation of continuous surface cell layers.

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PubMed1993

Loss of function of the Drosophila zfh-1 gene results in abnormal development of mesodermally derived tissues.

The Drosophila zfh-1 gene encodes an unusual protein with nine Cys2His2 type zinc-finger motifs and one homeodomain that shows a complex pattern of expression in the embryonic mesoderm and nervous system. To study the function of zfh-1, we generated loss-of-function zfh-1 mutations. Phenotypic analysis of zfh-1 mutant embryos reveals that the gene is not required for the initial segregation of the mesoderm or for the differentiation of mesodermally derived tissues. Rather, loss of zfh-1 function results in various degrees of local errors in cell fate or positioning.

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PubMed1993

Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis.

In the Drosophila embryo, motor neurons form stereotyped synapses (neuromuscular junctions) on identified muscles. We have used a mutant (prospero) that removes or delays innervation to assay the role of the presynaptic motor neuron in the development of the receptive field of the postsynaptic muscle. prospero (pros) is not expressed in the muscles or their precursors. Here we find that the muscle defines the correct synaptic zone in the absence of the motor neuron by restricting putative guidance molecules to this specialized membrane region. Furthermore, the muscle expresses functional transmitter receptors at the correct developmental time without innervation. On the other hand, the muscle does not localize receptors to the synapse without instruction from the motor neuron, nor does a second, much larger, synthesis of receptors occur in muscles deprived of innervation. In muscles receiving delayed innervation, or muscles innervated at aberrant synaptic sites, both receptor clustering and receptor synthesis are delayed or redirected, consistent with the new pattern of innervation. We conclude that the muscle autonomously defines the synaptic site, whereas the motor neuron directs the development of the muscle's receptive field by stimulating the synthesis and localization of transmitter receptors.

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PubMed1993

A wingless-dependent polar coordinate system in Drosophila imaginal discs.

The patterning of the imaginal discs in Drosophila melanogaster is a progressive process that, like the patterning of the larval epidermis during embryogenesis, requires the activity of segment polarity genes. One segment polarity gene, wingless, encodes a homolog of the mouse proto-oncogene Wnt-1 and plays a prominent role in the patterning of the larval epidermis and the imaginal discs. However, whereas the function of wingless in the embryo is initially associated with a pattern of stripes along the anteroposterior axis that are part of a Cartesian coordinate system, it is shown here that during imaginal development wingless is associated with a pattern of sectors that provide references for a polar coordinate system homologous to that postulated in a well-known model for the regeneration of insect and vertebrate limbs.

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PubMed1993

Activity-dependent development of the neuromuscular synapse during Drosophila embryogenesis.

In Drosophila, mutations in specific ion channel genes can increase or decrease the level of neural/synaptic activity. We have used these genetic tools, in combination with classical pharmacological agents, to modulate neural activity during embryogenesis and examined effects on the differentiation of an identified neuromuscular junction. We find that electrical activity is required for the neural induction of transmitter receptor expression during synaptogenesis. Likewise, neural electrical activity is required to localize transmitter receptors to the synaptic site. In muscles with activity-blocked synapses, a low level of receptors is expressed homogeneously in the muscle membrane as in muscles developing without innervation. Thus, presynaptic electrical activity is required to mediate the neural induction of the transmitter receptor field in the postsynaptic membrane.

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PubMed1993

Muscle development is independent of innervation during Drosophila embryogenesis.

We have examined the role of innervation in directing embryonic myogenesis, using a mutant (prospero), which delays the pioneering of peripheral motor nerves of the Drosophila embryo. In the absence of motor nerves, myoblasts fuse normally to form syncytial myotubes, myotubes form normal attachments to the epidermis, and a larval musculature comparable to the wild-type pattern is generated and maintained. Likewise, the twist-expressing myoblasts that prefigure the adult musculature segregate normally in the absence of motor nerves, migrate to their final embryonic positions and continue to express twist until the end of embryonic development. In the absence of motor nerves, myotubes uncouple at the correct developmental stage to form single cells. Subsequently, uninnervated myotubes develop the mature electrical and contractile properties of larval muscles with a time course indistinguishable from normally innervated myotubes. We conclude that innervation plays no role in the patterning, morphogenesis, maintenance or physiological development of the somatic muscles in the Drosophila embryo.

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