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L I Held

Publications and source records attributed to L I Held.

9 recordsLinked to original sources
PubMed1995

Axes, boundaries and coordinates: the ABCs of fly leg development.

Recent studies of gene expression in the developing fruitfly leg support a model--Meinhardt's Boundary Model--which seems to contradict the prevailing paradigm for pattern formation in the imaginal discs of Drosophila--the Polar Coordinate Model. Reasoning from geometric first principles, this article examines the strengths and weaknesses of these hypotheses, plus some baffling phenomena that neither model can comfortably explain. The deeper question at issue is: how does the fly's genome encode the three-dimensional anatomy of the adult? Does it demarcate territories and boundaries (as in a geopolitical map) and then use those boundaries and their points of intersection as a scaffolding on which to erect the anatomy (the Boundary Model)? Or does it assign cellular fates within a relatively seamless coordinate system (the Polar Coordinate Model)? The existence of hybrid Cartesian-polar models shows that the alternatives may not be so clear-cut: a single organ might utilize different systems that are spatially superimposed or temporally sequential.

Animals↗
PubMed1993

Segment-polarity mutations cause stripes of defects along a leg segment in Drosophila.

Various lines of evidence suggest that "segment-polarity" genes, which participate in segmenting the Drosophila embryo, may also play a role in the development of adult structures. Wilkins and Gubb (1991, Dev. Biol. 145, 1-12) have proposed that these genes specify the angular component of the polar coordinate system for each imaginal disc. If true, then segment-polarity mutations should cause abnormal patterning within well-defined sectors of the discs. To test this prediction, a leg segment was used where abnormalities can be precisely identified. The second-leg basitarsus bears eight rows of mechanosensory bristles, plus five chemosensory bristles between specific rows. Abnormalities were sought in the basitarsi of six different segment-polarity mutants and their 15 pairwise compounds. Consistent with the prediction, sectorial defects were indeed found: (1) deletions of specific rows (or chemosensory bristles) or portions thereof and (2) increased bristle number within (or between) specific rows. Both types of abnormalities were associated with changes in the widths of various parts of the circumference, implying that the alterations in bristle patterning may be mediated by regional perturbations of growth.

Animals↗
PubMed1993

The spatial organization of epidermal structures: hairy establishes the geometrical pattern of Drosophila leg bristles by delimiting the domains of achaete expression.

The spatial organization of Drosophila melanogaster epidermal structures in embryos and adults constitutes a classic model system for understanding how the two dimensional arrangement of particular cell types is generated. For example, the legs of the Drosophila melanogaster adult are covered with bristles, which in most segments are arranged in longitudinal rows. Here we elucidate the key roles of two regulatory genes, hairy and achaete, in setting up this periodic bristle pattern. We show that achaete is expressed during pupal leg development in a dynamic pattern which changes, by approximately 6 hours after puparium formation, into narrow longitudinal stripes of 3-4 cells in width, each of which represents a field of cells (proneural field) from which bristle precursor cells are selected. This pattern of gene expression foreshadows the adult bristle pattern and is established in part through the function of the hairy gene, which also functions in patterning other adult sense organs. In pupal legs, hairy is expressed in four longitudinal stripes, located between every other pair of achaete stripes. We show that in the absence of hairy function achaete expression expands into the interstripe regions that normally express hairy, fusing the two achaete stripes and resulting in extra-wide stripes of achaete expression. This misexpression of achaete, in turn, alters the fields of potential bristle precursor cells which leads to the misalignment of bristle rows in the adult. This function of hairy in patterning achaete expression is distinct from that in the wing in which hairy suppresses late expression of achaete but has no effect on the initial patterning of achaete expression. Thus, the leg bristle pattern is apparently regulated at two levels: a global regulation of the hairy and achaete expression patterns which partitions the leg epidermis into striped zones (this study) and a local regulation (inferred from other studies on the selection of neural precursor cells) that involves refinement steps which may control the alignment and spacing of bristle cells within these zones.

Animals↗
PubMed1991

Bristle patterning in Drosophila.

The 5000 bristles that protrude from the cuticle of a Drosophila adult function as either mechanosensors or chemosensors, and they are arranged in surprisingly intricate patterns. Development of the patterns appears to involve five stages: (1) establishment of a coordinate system of 'positional information'; (2) partitioning of the epidermis into areas where bristles either can or cannot originate; (3) selection of one or more bristle mother cells within each permissible area; (4) suppression of bristle development in the neighborhood of each mother cell; and (5) differentiation of the mother cell to produce four or more descendant cells, each of which forms part of the bristle apparatus. Some of the genes that control these events participate in more than one stage, and others play key roles in seemingly unrelated developmental pathways, including embryonic neurogenesis, body segmentation, and sex determination.

Animals↗
PubMed1990

Defective gap-junctional communication associated with imaginal disc overgrowth and degeneration caused by mutations of the dco gene in Drosophila.

The lethal(3)discs overgrown (dco) locus of Drosophila melanogaster, located on the third chromosome at cytogenetic position 100A5,6-100B1,2, is necessary for normal development and growth control in the imaginal discs of the larva. Three recessive lethal alleles (dco2, dco3, and dco18) in heteroallelic combinations and one allele (dco3) when homozygous cause the imaginal discs to continue to grow beyond the normal disc-intrinsic limit during an extended larval period. Some degeneration also occurs in the overgrowing discs. The discs overgrow even when transplanted early in their development into wild-type hosts, whereas normal discs stop growth at about the normal final size under such conditions, indicating that the overgrowth is a disc-autonomous effect of the mutations. During overgrowth the imaginal discs retain their single-layered epithelial structure except near regions of degeneration, and they differentiate into disc-appropriate but abnormal adult structures when transplanted into wild-type larval hosts. When the mutant larvae are reared under certain conditions a small percentage develop to the pharate adult stage, and these animals show a characteristic syndrome of abnormalities including swollen leg segments with many extra bristles, small or missing eyes, duplicated antennae and palpi, and separated vesicles of cuticle. A fourth recessive lethal allele (dcole88), when homozygous or in heteroallelic combination with the overgrowth alleles, causes the imaginal discs to degenerate, producing a "discless" phenotype. Gap junction-mediated communication was assayed by observing the intercellular transfer of injected fluorescein complexon (dye coupling). Dye coupling in the imaginal discs of the dco genotypes that cause overgrowth was dramatically reduced at 4 days after egg laying (AEL) compared with wild-type controls. Coupling was more normal although still significantly reduced at 7-8 and 12-14 days AEL. In c43hs1, another disc overgrowth mutant, the imaginal disc cells also showed very reduced dye coupling at 4 days and incomplete coupling at 9 days. In contrast, discs from wild-type larvae, two other imaginal disc overgrowth mutants, and a cell death mutant showed extensive dye coupling at all stages tested. Electron microscopic morphometry revealed a reduction in gap-junction length per unit lateral plasma membrane length in dco3/dco18 and c43hs1 wing discs, although not in dco2/dco3, compared with wild-type wing discs. The results suggest that gap-junctional cell communication may be involved in the cell interactions that limit cell proliferation in vivo.

Alleles↗
PubMed1988

Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila.

Lethal mutations at the fat locus in Drosophila cause imaginal discs to continue to grow by cell proliferation far beyond their normal final size. During a greatly extended larval period, the overgrowing imaginal discs develop additional folds and lobes, but retain a single-layered epithelial structure. In the wing disc, the additional lobes originate in the proximal fold area, and in the extra tissue the cells are less columnar than normal. Mutant disc cells lack zonulae adherents as well as associated microtubules and microfilaments, and they show an abnormal distribution and reduced density of gap junctions. The effect on growth is disc-autonomous as shown by transplantation experiments. The overgrown imaginal discs retain the ability to differentiate adult cuticular structures, as shown by metamorphosis of discs after transplantation into wild-type larval hosts and by the ability of some mutant animals to develop to the pharate adult stage. The structures differentiated by mutant discs show many abnormalities including ingrowths, outgrowths, separated cuticular vesicles, and areas of reversed bristle polarity; some of these abnormalities suggest that the mutations interfere with cell adhesion as well as the control of cell proliferation. The fat locus is located in cytogenetic interval 24D5.6-7, and 18 alleles are known including spontaneous, chemically induced, X-ray-induced, and dysgenic mutations.

Alleles↗
PubMed1982

Polyploidy and aneuploidy induced by colcemid in Drosophila melanogaster.

Colcemid was fed to Drosophila melanogaster larvae throughout most of the larval period. Surviving individuals were then mated with untreated flies, and their progeny were examined for polyploid flies or flies resulting from X-chromosome nondisjunction. A total of 251 polyploid offspring was recovered from the experimental matings, none from the control. All of the polyploids were evidently triploids, and all but one were obtained from colcemid-fed females: males produced significantly lower frequencies of triploid offspring than females. The highest average frequency of triploid offspring obtained from any treatment group was 18%. Nonrandom distributions of triploid offspring were observed among females raised identically, indicating tht polyploidization occurs mitotically, rather than meiotically, giving rise to clones of tetraploid oogonia. 9 colcemid-fed females produced exclusively triploid offspring. Colcemid also caused a significant increase in X-chromosome nondisjunction in females, though the frequencies of such offspring were at least several-fold lower than the frequencies of triploid offspring. Somatic polyploidy was apparently also indiced since patches of large cells were found on the wings of some flies raised on colcemid-containing food. Various teratological abnormalities were observed among the treated flies, including deformed or missing eyes and partially duplicated thoraxes.

Abnormalities, Drug-Induced↗