Biomedical subjects

W J Brook

Publications and source records attributed to W J Brook.

7 recordsLinked to original sources

PubMed1996

Antagonistic interactions between wingless and decapentaplegic responsible for dorsal-ventral pattern in the Drosophila Leg.

Subdivision of the limb primordia of Drosophila into anterior and posterior compartments triggers cell interactions that pattern the legs and wings. A comparable compartment-based mechanism is used to pattern the dorsal-ventral axis of the wing. Evidence is presented here for a mechanism based on cell interaction, rather than on compartment formation, that distinguishes dorsal from ventral in the leg. Mutual repression by Wingless and Decapentaplegic signaling systems generates a stable regulatory circuit by which each gene maintains its own expression in a spatially restricted domain. Compartment-independent patterning mechanisms may be used by other organisms during development.

Animals↗

PubMed1996

Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing.

Secreted signalling molecules provide cells with positional information that organizes long-range pattern during the development of multicellular animals. Evidence is presented that localized expression of Decapentaplegic instructs cells about their position along the anterior-posterior axis of the Drosophila wing in two distinct ways. One mechanism is based on the local concentration of the secreted protein; the other is based on the ability of the cells to retain an instruction received at an earlier time when their progenitors were in close proximity to the signal. Both mechanisms are involved in axis formation.

Animals↗

PubMed1996

Organizing spatial pattern in limb development.

Recent studies on the development of the legs and wings of Drosophila have led to the conclusion that insect limb development is controlled by localized pattern organizing centers, analogous to those identified in vertebrate embryos. Genetic analysis has defined the events that lead to the formation of these organizing centers and has led to the identification of gene products that mediate organizer function. The possibility of homology between vertebrate and insect limbs is considered in light of recently reported similarities in patterns of gene expression and function.

Animals↗

PubMed1995

Distinguishable functions for engrailed and invected in anterior-posterior patterning in the Drosophila wing.

Subdivision of the limb primordia into compartments initiates pattern formation in the developing limbs. Interaction between distinctly specific cells in adjacent compartments leads to localized expression of the secreted signalling molecules Wingless (Wg) or Decapentaplegic (Dpp), which in turn organize pattern and control growth of the limbs. The homeobox gene engrailed has been implicated in specification of posterior cell fate, whereas the LIM/homeobox gene, apterous, specifies dorsal fate. Removing apterous activity causes a complete transformation from dorsal to ventral fate and leads to the formation of an ectopic dorsal-ventral boundary organizer. By contrast, removing engrailed activity causes incomplete morphological transformation from posterior to anterior fate in the wing, and fails to produce an ectopic anterior-posterior organizer (reviewed in ref.2). Complete transformation can only be effected by simultaneously eliminating activity of engrailed and its homologue invected. Here we show that invected functions principally to specify posterior cell fate. Thus establishment of the anterior-posterior organizer and control of compartment identity are genetically distinguishable, and invected may perform a discrete subset of functions previously ascribed to engrailed.

Animals↗

PubMed1995

Analysis of an enhancer trap expressed in regenerating Drosophila imaginal discs.

In Drosophila, imaginal discs are the undifferentiated larval precursors of the pattern of epidermal and sensory neural cells in each adult segment. Although cell fates are already specified by late third instar, disc fragments can either regenerate or duplicate after growth in culture. The outcome depends on signaling between cells across the healed wound and involves a redeployment of the expression patterns of selector genes and other disc pattern genes. We recently used the enhancer-trap method to screen for such genes that are expressed ectopically at the wound-heal site in imaginal discs undergoing regeneration. Here we report the cloning by plasmid rescue of transcribed sequences adjacent to one such enhancer-trap insertion. Using Northern analysis and in situ hybridization we show that one transcript is expressed in the embryo and in imaginal discs in a pattern similar to that of the enhancer trap. We also, by imprecise excision of the enhancer-trap insertion, generated a series of flanking deletions that were mapped using Southern analysis and complementation.

Animals↗

PubMed1993

Gene expression during imaginal disc regeneration detected using enhancer-sensitive P-elements.

When imaginal disc fragments from Drosophila are cultured in adult female hosts, they either duplicate the part of the pattern specified by the fate map, or regenerate to replace the missing part. The new tissue is added by proliferation of a small number of cells from the cut edge, brought together when the wound heals to form a regeneration blastema. Specification of the new pattern has been explained by assuming interactions among cells of different positional value in the regeneration blastema. In order to identify genes which might mediate these events, we screened over eight hundred independently isolated autosomal insertions of an enhancer-sensitive P-element, for altered lac-z expression in regenerating discs following cell death induced by a temperature-sensitive cell-lethal mutation. Two further screens divided the positive lines into four groups based on appropriate timing of the lac-z response in the cell-lethal mutant background and the expected response to an alternate source of cell death. Expression in wing disc fragments cultured in vivo was most frequent in the target class defined by the screens. In this direct test, lac-z expression was found in 23 lines and in most cases was spatially and temporally correlated with the formation of the regeneration blastema. Our results suggest a very substantial transcriptional response during the early stages of imaginal disc regeneration. lac-z expression in control imaginal discs, embryos and adult ovaries of the positive lines was also assayed. The selected insertions included: a small class expressed only in discs undergoing regeneration and apparently not at any other stage, possibly representing genes active exclusively in regeneration; a larger class expressed in the embryo or during oogenesis, but not normally in imaginal discs, as expected for functions recruited from earlier stages of the developmental program; and finally a class with spatially patterned expression in normal discs. This class included several insertions with expression associated with compartment boundaries, including one at the decapentaplegic (dpp), and one at the crumbs (crb) locus, a growth factor homologue, and an EGF-repeat gene respectively. Some of the expression patterns observed in cultured disc fragments provide evidence for cell communication in the regeneration blastema.

Animals↗

PubMed1990

Genetic and molecular analysis of vgU and vgW: two dominant vg alleles associated with gene fusions in Drosophila.

In the absence of a vg+ gene, extensive cell death occurs in third instar imaginal discs, which results in a complete loss of adult wing margin structures. Essentially all molecularly characterized vg alleles are associated with deletions or insertions of DNA into the vg locus. These alterations reduce or eliminate a 3.8-kb vg-specific transcript, resulting in recessive loss of function alleles. We report here the analysis of two dominant vg alleles which have been identified (vgU and vgW). The vgU allele is associated with a chromosomal inversion which splits the vg locus, resulting in a gene fusion between vg and the mastermind (mam) neurogenic locus. Reversion analysis of vgU indicates that sequences from the mam locus are required for vgU dominance. The vgW allele is also the result of a chromosomal inversion, in this case resulting in a gene fusion between vg and the homeobox-containing invected (inv) gene. It is also associated with novel dominant homeotic transformations. Revertant analysis indicates that sequences from inv are required for the dominant wing and dominant homeotic effects of vgW. The vg dominance does not appear to be mediated through a reduction of vg expression or a novel fusion transcript in either vgU or vgW. The results are consistent with a model in which inappropriate expression of inv causes the dominant homeotic effects seen in vgW.

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