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M Heisenberg

Publications and source records attributed to M Heisenberg.

At least 19 recordsLinked to original sources

The lethal(1)optomotor-blind gene of Drosophila melanogaster is a major organizer of optic lobe development: isolation and characterization of the gene.

The X-chromosomal complementation unit lethal(1)optomotor-blind [l(1)omb] is defined by lack of complementation among over a dozen recessive lethal mutations that map to the omb gene locus. Mutations in l(1)omb also fail to complement viable mutations of three seemingly unrelated functions in this region: bifid (bi), manifesting defective wings, Quadroon (Qd), a semi-dominant mutation expressing abnormal tergite pigmentation, and In(1)ombH31, giving rise to a normal external morphology but with discrete defects in the optic lobes and behavior. The locus encodes a 70-kilobase primary transcript that is spliced into a 6-kilobase mature RNA. cDNAs for this transcript were isolated and sequenced and the derived amino acid sequence was analyzed. Certain features of this sequence suggest that the l(1)omb gene product is a nuclear regulatory protein. The lethal phase of various apparent null mutants was determined and found to occur mainly in the pupal stage. A large proportion of all hemizygous mutant males develop to pharate adults that eclose only rarely but can be rescued from the pupal case. These animals show a severe maldevelopment of the optic lobes. In addition they have only rudimentary wings as well as a Quadroon-like abdominal pigmentation. Thus, in the lethal mutants those parts of the body are affected for which independent viable mutations have been previously described in the omb locus, such as optomotor-blind, bifid, and Quadroon.

Amino Acid Sequence

Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.

Mutations in the Drosophila gene giant lens (gil) affect ommatidial development, photoreceptor axon guidance and optic lobe development. We have cloned the gene using an enhancer trap line. Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif. We have generated mutations at the gil locus by imprecise excision of the enhancer trap P-element. In the absence of gil, additional photoreceptors develop at the expense of pigment cells, suggesting an involvement of gil in cell determination during eye development. In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development. In wildtype flies, photoreceptor axons grow from the eye disc through the optic stalk into the larval brain hemisphere, where retinal innervation is required for the normal development of the lamina and distal medulla. The projection pattern of these axons in the developing lamina and medulla is highly regular and reproducible. In gil, photoreceptor axons enter the larval brain but fail to establish proper connections in the lamina or medulla. We propose that gil encodes a new type of signalling molecule involved in the process of axon pathfinding and cell determination in the visual system of Drosophila.

Amino Acid Sequence

No-bridge of Drosophila melanogaster: portrait of a structural brain mutant of the central complex.

The mutant no-bridge (nobKS49) has its name from a structural defect in the protocerebral bridge of the central complex. This rod-shaped neuropil in nobKS49 has a large gap at the sagittal midplane, with some of the missing material accumulated more laterally. Mutant nob flies have a reduced maximal and average walking speed. Leg coordination is disturbed during turning but not while walking straight. Motivation for walking is low and steps are small due to slow forward swinging of the legs. Flies spontaneously may pass into an autistic (and possibly spastic) state in which they can move their legs and even perform cleaning movements but do not walk or fly. They spontaneously recover if left undisturbed. Gynandromorph experiments place the focus of the walking defects into the head. Mutant flies have a reduced tendency to escape when mechanically stimulated. In a brightly lit arena they do not avoid a black square above the horizon and they are negatively phototactic. In tethered flight optomotor responses are normal but the amplitude of spontaneous torque modulations as well as the number of torque spikes are reduced. If a single black bar is slowly rotated around the fly, the normal response pattern is observed. It vanishes, however, at moderately fast angular velocity at which the wild type still is fully responsible. The behavioral defects support the notion that the protocerebral bridge is part of a higher center for the regulation of behavior.

Animals

Mutations in the proximal region of the optomotor-blind locus of Drosophila melanogaster reveal a gradient of neuroanatomical and behavioral phenotypes.

Mutations in the complex optomotor-blind (omb) gene locus (4C4-6) lead to a number of different phenotypes in various tissues of the adult Drosophila melanogaster fly. At the core of the locus lies a lethal complementation group, named l(1)omb, whose mutations cause larval and pupal lethality. Some 40% of all males hemizygous for lethal omb alleles develop to the pharate adult stage. These flies can be rescued from the pupal case and show a severe disturbance in optic lobe development. The recessive viable allele In(1)ombH31 reduces the optomotor response in walking flies and during stationary flight of tethered flies. At the neuroanatomical level, these animals lack a subset of lobula plate giant neurons (LPGNs), which are thought to mediate optomotor behavior. Chromosomal aberrations deleting the proximal, non transcribed part of the locus complement the lethality, but still cause neuroanatomical and optomotor defects. Analysis of different allelic combinations of such mutations, in which increasing amounts of DNA downstream of the transcribed region are removed, reveals a step gradient of increasing severity of the neuroanatomical defects and behavioral phenotypes. On this basis the 3'-regulatory region is divided into three domains each having specific effects on optic lobe development.

Alleles

Basic organization of operant behavior as revealed in Drosophila flight orientation.

Operant behavior is studied in tethered Drosophila flies using visual motion, heat or odour as operandum and yaw torque, thrust or direction of flight as operans in various combinations (Fig. 1). On the basis of these results a conceptual framework of operant behavior is proposed: (1) It requires a goal (desired state) of which the actual state deviates. (2) To attain the goal a range of motor programs is activated (initiating activity, see Fig. 7). (3) Efference copies of the motor programs are compared to the sensory input referring to the deviation from the desired state (e.g. by cross-correlation). (4) In case of a significant coincidence the respective motor program is used to modify the sensory input in the direction towards the goal. (5) Consistent control of a sensory stimulus by a behavior may lead to a more permanent behavioral change (conditioning). In this scheme operant activity (1-4) and operant conditioning (1-5) are distinguished.

Animals

Identification of H1 visual interneuron in Drosophila by [3H]2-deoxyglucose uptake during stationary flight.

High-resolution 2-deoxyglucose (2-DG) neuronal activity labeling is used to identify a visual interneuron in Drosophila by its stimulus-specific uptake of [3H]2-DG during stationary flight in a well-characterized behavioral situation. With a single rotating stripe as visual stimulus a neuron is heavily labeled that has not been described in Drosophila before but is homologous to the extensively studied H1 visual interneuron of larger diptera. Labeling of this cell is inconspicuous in Drosophila if the animal is stimulated with a rotating striped drum.

Animals

Visual control of straight flight in Drosophila melanogaster.

The optomotor system of Drosophila is investigated in a flight simulator in which the fly's yaw torque controls the angular velocity of the panorama (striped drum, negative feedback). Flies in the flight simulator maintain a stable orientation even in a homogeneously textured panorama without landmarks. During 'straight' flight, torque is not zero. It consists of small pulses mostly alternating in polarity. The course is controlled by the duration (and possibly amplitude) of the pulses. The system operates under reafference control. By comparing the pulses with the visual input the system continuously measures and adjusts the efficacy of the torque output. The comparison, however, is not between angular velocity and yaw torque but, instead, between visual acceleration and pretorque, the first time derivative of torque. For comparison, the system first computes a cross-correlation. If the correlation coefficient is above a certain threshold the system calculates the external gain and adjusts its internal gain so as to keep the total gain constant. With the correlation coefficient below threshold, however, the system keeps the internal gain low despite the infinitely small external gain. We propose that for a reafferent optomotor system the coupling coefficient and the correlation coefficient of pretorque and visual acceleration are more relevant than the distinction between exafference and reafference.

Animals

Coordination of legs during straight walking and turning in Drosophila melanogaster.

Leg coordination of Drosophila melanogaster was studied using frame-by-frame film analysis. 1. For fastest walking alternating tripod coordination is observed which slightly deviates towards tetrapody as a function of step period. During acceleration or deceleration legs may transiently recover in diagonal pairs. 2. Mean step length increases with step frequency. 3. Mean recovery stroke duration increases with step period and plateaus beyond a period of about 110 ms. Middle legs recover significantly faster than others. 4. Ipsilateral footprints are transversally separated. 5. Walking is usually initiated in tripod coordination (frequently in combination with a turn), otherwise in an accelerating sequence which rapidly shifts towards tripod pattern. Flies can stop abruptly or decelerate over about one metachronal wave. 6. Short interruptions in walking are observed. Legs interrupted during swing phase stay lifted and finish recovery thereafter. 7. Slight changes in walking direction are obtained by altering step lengths only. Tight turns are composed of two or three phases with backward, zero and forward translatory components. In fast turning tripod coordination is maintained. Otherwise body sides can decouple widely. In all turns numbers of contralateral metachronal waves were equal. Results are compared to those for other walking insects and their relevance in screens for locomotor mutants is discussed.

Animals

Genetic and molecular characterization of the optomotor-blind gene locus in Drosophila melanogaster.

The Drosophila gene optomotor-blind (omb) is involved in the development of a set of giant neurons in the optic lobes and possibly other structures in the imaginal brain. Adult flies have discrete defects in optomotor behavior. The gene has previously been mapped in chromomeres 4C5-6, together with three other genes, bifid, Quadroon and lacqueredgls. We have localized the gene in a genomic walk of 340 kb of DNA. By mapping seven chromosome breakpoints with omb phenotype we determined its minimum size to about 80 kb. From this region more than 20 RNAs of different size and temporal expression pattern are transcribed. Three of them (T3, T7 and T7') stem from primary transcripts of 40-80 kb in length. In its distal part the omb gene overlaps in at least 19 kb with four other complementation units, bifid, l(1)bifid, Quadroon and lacqueredgls. The three nonlethals affect the external appearance of the fly and seem to be unrelated to brain development.

Animals

Are the structural changes in adult Drosophila mushroom bodies memory traces? Studies on biochemical learning mutants.

The pre-imaginal development of Drosophila mushroom bodies is under the influence of an unknown variable which causes populations of wild-type flies at eclosion to differ in the average number of Kenyon cell fibers. During the first week of adult life the number of adjusts to an intermediate level which depends upon the experience of the flies. Under olfactory deprivation or social isolation it reaches a lower level than under favorable rearing conditions (J. Neurogenet., 1 (1984) 113-126). The biochemical learning mutants dunce and rutabaga show no experience-dependent modulation of fiber number. In both strains the mushroom bodies of young adults seem to develop abnormally: in dunce a loss of about 600 fibers is observed, in rutabaga fiber number is low at eclosion and does not increase. The following model for long-term memory is proposed: in mushroom bodies outgrowth and decay of Kenyon cell fibers occur simultaneously. The fibers randomly form transient synapses onto extrinsic output neurons of the mushroom bodies and receive synapses from modulating neurons. Experience consolidates certain synapses, thus prolonging survival of the respective Kenyon cell fibers and increasing the steady state level of fiber number.

Animals

The structural brain mutant Vacuolar medulla of Drosophila melanogaster with specific behavioral defects and cell degeneration in the adult.

The mutant Vam (Vacuolar medulla) has vacuoles in the distal medulla, caused by age-dependent cell degeneration in the lamina and the medulla. Lamina monopolar neurons L1 and L2 degenerate, but whether the degeneration is confined only to these cells is uncertain. The cell degeneration commences at eclosion and the vacuoles begin appearing about 1/2 h after eclosion. This is accompanied by the disappearance of the electroretinogram transients and a loss of the optomotor response. Vam males or homozygous Vam females one day after eclosion or later, show no measurable optomotor response to horizontal or vertical movement and no landing response. However, they are able to turn towards dark stripes larger than 20 degrees in width. This indicates that motion-dependent visual responses are not a prerequisite for landmark fixation in Drosophila. The mutant's apparent defects suggest that the loss of motion-dependent visual functions is due to the loss of certain cell types linking the lamina to the distal medulla. The role of lamina neurons in optomotor responses and fixation behavior is discussed.

Animals

Genetic dissection of optomotor behavior in Drosophila melanogaster. Studies on wild-type and the mutant optomotor-blindH31.

In stationary flight Drosophila melanogaster produces yaw torque in response to visual movement stimuli. The residual optomotor yaw torque response of the mutant optomotor-blindH31 (omb), which lacks the horizontal (HS) and vertical (VS) giant fibers in the lobula plate, differs from that of wild-type in several aspects: it is restricted to the frontal visual field, it is only elicited by front-to-back motion and appears to be mediated by a different set of elementary movement detectors (EMDs). Using a single black stripe as motion stimulus the torque response is, even in wild-type flies, dominated by the frontal visual field and by front-to-back motion. We thus propose that Drosophila's optomotor yaw control is organized as two partially parallel subunits. The component still displayed by omb is called "object response"; the component missing in the mutant (which is presumably mediated by the giant HS-cells in the wild-type) is called "large field response". Several properties of the object response are described.

Animals

Drosophila mushroom body mutants are deficient in olfactory learning.

Two Drosophila mutants are described in which the connections between the input to and the output from the mushroom bodies is largely interrupted. In all forms of the flies (larva, imago, male, female) showing the structural defect, olfactory conditioning is impaired. Learning is completely abolished when electroshock is used as reinforcement and partially suppressed in reward learning with sucrose. No influence of the mushroom body defect on the perception of the conditioning stimuli or on spontaneous olfactory behavior is observed. The defect seems not to impair learning of color discrimination tasks or operant learning involving visual cues.

Animals

Phycomyces.

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Cell Biology