Biomedical subjects

F J Diaz-Benjumea

Publications and source records attributed to F J Diaz-Benjumea.

10 recordsLinked to original sources

PubMed1998

Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function.

Formation of the dorsal-ventral axis of the Drosophila wing depends on activity of the LIM-homeodomain protein Apterous (Ap). Here we report that Ap activity levels are modulated by dLMO, the protein encoded by the Beadex (Bx) gene. Overexpression of dLMO in Bx mutants interferes with Apterous function. Conversely, Bx loss-of-function mutants fail to down-regulate Apterous activity at late stages of wing development. Biochemical analysis shows that dLMO protein competes for binding of Apterous to its cofactor Chip. These data suggest that Apterous activity depends on formation of a functional complex with Chip and that the relative levels of dLMO, Apterous, and Chip determine the level of Apterous activity. The dominant interference mechanism of dLMO action may serve as a model for the mechanism by which LMO oncogenes cause cancer when misexpressed in T cells.

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PubMed1996

Specification of the wing by localized expression of wingless protein.

Limb development in Drosophila depends on subdivision of the limb primordia into functional units called compartments. Cell interactions across compartment boundaries establish pattern-organizing centres that control growth and specify cell fates along the anteroposterior (AP) and dorsoventral (DV) axes of the limbs. AP subdivision of the disc primordia is inherited from the embryonic ectoderm. DV subdivision of the wing disc occurs during the second larval instar through localized expression of the apterous protein (Apterous) in dorsal cells. A third major subdivision of the wing disc into wing and body-wall compartments also occurs in the second instar. Here we show that specification of the wing primordium in early second instar depends on activity of the AP patterning system but not the DV system. These results define two distinct roles for the wingless gene: a primary role in specifying the wing primordium, and a subsequent role mediating the patterning activities of the DV compartment boundary.

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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.

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PubMed1995

Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning.

Interaction between distinctly specified cells in adjacent compartments establishes organizing centres that control growth and specify cell fate in the developing limbs of Drosophila. Localized expression of the secreted Hedgehog protein (Hh) by cells in the posterior compartment induces expression of the secreted signalling molecules decapentaplegic (dpp) or wingless (wg) in nearby anterior cells. wg and dpp in turn organize spatial pattern in the wing and leg imaginal discs. The Hh signal is thought to act by antagonizing the ability of the patched (ptc) gene product to repress wg and dpp expression. Here we present evidence that removing activity of the gene encoding cyclic AMP-dependent protein kinase A (pka) is functionally equivalent to removing ptc activity or to providing cells with the Hh signal. These findings suggest that cyclic AMP-dependent protein kinase A is a component of the signal transduction pathway through which Hh and Ptc direct localized expression of dpp (or wg) and establish the compartment boundary organizer.

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PubMed1995

Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing.

Growth and patterning of the Drosophila wing is controlled by organizing centers located at the anterior-posterior and dorsal-ventral compartment boundaries. Interaction between cells in adjacent compartments establish the organizer. We report here that Serrate and Notch mediate the interaction between dorsal and ventral cells to direct localized expression of Wingless at the D/V boundary. Serrate serves as a spatially localized ligand which directs Wg expression through activation of Notch. Ligand independent activation of Notch is sufficient to direct Wg expression, which in turn mediates the organizing activity of the D/V boundary.

Animals↗

PubMed1995

Nubbin encodes a POU-domain protein required for proximal-distal patterning in the Drosophila wing.

The nubbin gene is required for normal growth and patterning of the wing in Drosophila. We report here that nubbin encodes a member of the POU family of transcription factors. Regulatory mutants which selectively remove nubbin expression from wing imaginal discs lead to loss of wing structures. Although nubbin is expressed throughout the wing primordium, analysis of genetic mosaics suggests a localized requirement for nubbin activity in the wing hinge. These observations suggest the existence of a novel proximal-distal growth control center in the wing hinge, which is required in addition to the well characterized anterior-posterior and dorsal-ventral compartment boundary organizing centers.

Animals↗

PubMed1994

Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs.

The appendage primordia of Drosophila are subdivided into compartments by the localized expression of transcription factors. Interaction between cells in adjacent compartments establishes organizing centres responsible for generating spatial pattern and promoting cell proliferation in the developing appendages. Localized expression of hedgehog (hh) in the posterior compartment of the leg imaginal disc directs expression of wingless (wg) in ventral-anterior cells and decapentaplegic (dpp) in dorsal-anterior cells near the anterior-posterior compartment boundary; wg then acts to specify ventral cell fate and to organize the dorsal-ventral axis of the leg. Interaction between wg-expressing ventral cells and dorsal cells near the anterior-posterior compartment boundary promotes axis formation in the leg. Here we show that the combined action of wg-expressing cells in the ventral-anterior compartment and dpp-expressing cells in the dorsal-anterior compartment activates expression of Distal-less, a gene required for proximal-distal axis formation in the limbs. These results demonstrate that sequential interaction between anterior-posterior and dorsal-ventral compartments establishes the proximal-distal axis of the limbs.

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PubMed1994

The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development.

In Drosophila, Drk, an SH2 adaptor protein, Sos, a putative activator of Ras1, Ras1, raf and rolled/MAP kinase have been shown to be required for signalling from the sevenless and the torso receptor tyrosine kinase. From these studies, it was unclear whether these components act in a single linear pathway as suggested by the genetic analysis or whether different components serve to integrate different signals. We have analyzed the effects of removing each of these components during the development of the adult epidermal structures by generating clones of homozygous mutant cells in a heterozygous background. Mutations in each of these signalling components produce a very similar set of phenotypes. These phenotypes resemble those caused by loss-of-function mutations in the Drosophila EGF receptor homolog (DER). It appears that these components form a signalling cassette, which mediates all aspects of DER signalling but that is not required for other signalling processes during epidermal development.

Animals↗

PubMed1994

wingless acts through the shaggy/zeste-white 3 kinase to direct dorsal-ventral axis formation in the Drosophila leg.

The secreted glycoproteins encoded by Wnt genes are thought to function as intercellular signaling molecules which convey positional information. Localized expression of Wingless protein is required to specify the fate of ventral cells in the developing Drosophila leg. We report here that Wingless acts through inactivation of the shaggy/zeste white 3 protein kinase to specify ventral cell fate in the leg. Ectopic expression of Wingless outside its normal ventral domain has been shown reorganize the dorsal-ventral axis of the leg in a non-autonomous manner. Using genetic mosaics, we show that cells that lack shaggy/zeste white 3 activity can influence the fate of neighboring cells to reorganize dorsal-ventral pattern in the leg, in the same manner as Wingless-expressing cells. Therefore, clones of cells that lack shaggy/zeste white 3 activity exhibit all of the organizer activity previously attributed to Wingless-expressing cells, but do so without expressing wingless. We also show that the organizing activity of ventral cells depends upon the location of the clone along the dorsal-ventral axis. These findings suggest that Wingless protein does not function as a morphogen in the dorsal-ventral axis of the leg.

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PubMed1993

Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila.

The adult appendages of Drosophila develop from imaginal discs. An early step in disc patterning involves the formation of developmental boundaries that subdivide the discs into compartments. Anterior and posterior compartments are established in the embryo. Later in development a new boundary originates to subdivide the wing disc into dorsal and ventral compartments, which correspond to the dorsal and ventral surfaces of the adult wing. We report here that spatially localized expression of the homeobox gene apterous (ap) specifies the identity of dorsal cells in the wing. The boundary of cell lineage restriction between dorsal and ventral compartments coincides with the limit of the domain of ap expression. Using genetic mosaics, we show that juxtaposition of dorsal and ventral cells induces formation of the wing margin. We present evidence that the dorsal-ventral boundary promotes growth and serves as a pattern-organizing center in the wing disc.

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