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T Casci

Publications and source records attributed to T Casci.

17 recordsLinked to original sources
PubMed2001

A primary role for the epidermal growth factor receptor in ommatidial spacing in the Drosophila eye.

BACKGROUND: The differentiation of regularly spaced structures within an epithelium is a common feature of developmental pattern formation. The regular spacing of ommatidia in the Drosophila eye imaginal disc provides a good model for this phenomenon. The correct spacing of ommatidia is a central event in establishing the precise hexagonal pattern of ommatidia in the Drosophila compound eye. The R8 photoreceptors are the founder cells of each of the ommatidia that comprise the adult eye and are specified by a bHLH transcription factor, Atonal. RESULTS: We find that the epidermal growth factor receptor (Egfr) has a primary function in regulating R8 spacing. The receptor's activation within nascent ommatidia induces the expression of a secreted inhibitor that blocks atonal expression, and therefore ommatidial initiation, in nearby cells. The identity of the secreted inhibitor remains elusive but, contrary to previous suggestions, we show that it is not Argos. This Egfr-dependent inhibition acts in parallel to the inhibition of atonal by the secreted protein Scabrous. The activation of the Egfr pathway is dependent on Atonal function via the expression of Rhomboid-1. Our results also allow us to conclude that Egfr's role in promoting cell survival is largely independent of its role in photoreceptor recruitment; even when cell death is blocked, most photoreceptors fail to form. CONCLUSIONS: Based on our data and those of others, we propose a model for R8 spacing that comprises a self-organizing network of signaling molecules. This model describes how successive rows of ommatidia form out of phase with each other, leading to the hexagonal array of facets in the compound eye.

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PubMed1999

Sprouty, an intracellular inhibitor of Ras signaling.

Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells. Sprouty's function is, however, more widespread. We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling. In contrast to an earlier proposal that Sprouty is extracellular, we show by biochemical analysis that Sprouty is an intracellular protein, associated with the inner surface of the plasma membrane. Sprouty binds to two intracellular components of the Ras pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction.

Animals↗
PubMed1999

Control of EGF receptor signalling: lessons from fruitflies.

The EGF receptor, and the related ErbB family of receptor tyrosine kinases, have been much implicated in human cancer. Hyperactive receptor signalling promotes deregulated growth control and the onset of malignancy, as well as the disruption of developmental programmes. Very little, however, is known about ErbB physiological regulation in humans. The fruitfly, Drosophila melanogaster, has a single receptor homologous to the four ErbB receptors and in this review we discuss how a genetic approach has led to significant insights into how the fly receptor is regulated. As signalling mechanisms have been well conserved between flies and mammals, these results of experiments in flies are relevant to the study of the human receptors in development and disease. Two areas of recent progress are emphasised. First, a number of signal modulators have been identified, including three EGF receptor inhibitors, several of which have human homologues. Second, we describe how the signalling molecules are integrated into regulatory networks that specify the elaborate activation profiles needed in development--positive and negative feedback control of EGF receptor signalling emerges as a central theme. Although the study of the Drosophila EGF receptor has no direct clinical application, the mechanistic insight it provides suggests new avenues of more applied research, including potential therapeutic targets.

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