Feedback regulation is central to Delta-Notch signaling required for Drosophila wing vein margin

Program in Genetics, Cell and Developmental Biology, Department of Biology, Indiana University, Bloomington 47405, USA.
Development (Impact Factor: 6.46). 10/1997; 124(17):3283-91.
Source: PubMed


Delta and Notch are required for partitioning of vein and intervein cell fates within the provein during Drosophila metamorphosis. We find that partitioning of these fates is dependent on Delta-mediated signalling from 22 to 30 hours after puparium formation at 25 degrees C. Within the provein, Delta is expressed more highly in central provein cells (presumptive vein cells) and Notch is expressed more highly in lateral provein cells (presumptive intervein cells). Accumulation of Notch in presumptive intervein cells is dependent on Delta signalling activity in presumptive vein cells and constitutive Notch receptor activity represses Delta accumulation in presumptive vein cells. When Delta protein expression is elevated ectopically in presumptive intervein cells, complementary Delta and Notch expression patterns in provein cells are reversed, and vein loss occurs because central provein cells are unable to stably adopt the vein cell fate. Our findings imply that Delta-Notch signalling exerts feedback regulation on Delta and Notch expression during metamorphic wing vein development, and that the resultant asymmetries in Delta and Notch expression underlie the proper specification of vein and intervein cell fates within the provein.

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    • "Finally, there are several very well-characterized antibodies recognizing key components of the pathway. These include monoclonal antibodies targeting Notch and Delta [66–68]. Besides revealing the cell types that produce these key players, these antibodies have been used extensively for investigating the sub-cellular trafficking of these transmembrane proteins. "
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    ABSTRACT: Notch signaling involves a highly conserved pathway that mediates communication between neighboring cells. Activation of Notch by its ligands, results in the release of the Notch intracellular domain (NICD), which enters the nucleus and regulates transcription. This pathway has been implicated in many developmental decisions and diseases (including cancers) over the past decades. The simplicity of the Notch pathway in Drosophila melanogaster, in combination with the availability of powerful genetics, make this an attractive model for studying fundamental principles of Notch regulation and function. In this chapter we present some of the established and emerging tools that are available to monitor and manipulate the Notch pathway in Drosophila and discuss their strengths and weaknesses.
    Methods 04/2014; 68(1). DOI:10.1016/j.ymeth.2014.03.029 · 3.65 Impact Factor
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    • "In the eye, cells along the dorsal side of the midline co-express N and Dl while their counterparts along the ventral side of the midline co-express N and Ser. Similar receptorligand relationships are also seen in the developing wing and are thought to mediate a positive-feedback loop between cells that straddle the D/V border (Diaz-Benjumea, 1995; Huppert et al., 1997). In the eye the model is that Ser expression in the ventral compartment signals across the midline to induce Notch-dependent activation of Dl transcription. "
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    ABSTRACT: The compound eye of the fruit fly, Drosophila melanogaster, has for decades been used extensively to study a number of critical developmental processes including tissue development, pattern formation, cell fate specification, and planar cell polarity. To a lesser degree it has been used to examine the cell cycle and tissue proliferation. Discovering the mechanisms that balance tissue growth and cell death in developing epithelia has traditionally been the realm of those using the wing disc. However, over the last decade a series of observations has demonstrated that the eye is a suitable and maybe even preferable tissue for studying tissue growth. This review will focus on how growth of the retina is controlled by the genes and pathways that govern the specification of tissue fate, the division of the epithelium into dorsal-ventral compartments, the initiation, and progression of the morphogenetic furrow and the second mitotic wave.
    Developmental Neurobiology 12/2011; 71(12):1133-52. DOI:10.1002/dneu.20921 · 3.37 Impact Factor
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    • "Further restriction of the provein width from eight or nine-cells to two or three-cells requires the activation of the Notch pathway during the pupal stage. In lateral provein cells, the activation of receptor Notch (N) by its ligand Delta expressed in the central region leads to the suppression of vein cell differentiation [12,13]. In N loss-of-function mutants, lateral provein cells differentiate into vein fate, causing the widening of wing veins [14]. "
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    ABSTRACT: The conserved Notch signaling pathway regulates cell fate decisions and maintains stem cells in multicellular organisms. Up-regulation of Notch signaling is observed in several types of cancer and is causally involved in proliferation and survival of cancer cells. Thus, it is of great interest to look for anti-Notch reagents for therapeutic purposes. In model animal Drosophila, Notch signaling restricts selection of sensory organ precursors (SOPs) during external sensory (ES) organ development. To look for novel genes that can suppress Notch signaling, we performed a gain-of-function modifier screen to look for genes that enhance the phenotype of ectopic ES organs induced by overexpression of phyllopod, a gene required for SOP specification. From the gain-of-function screen, we discovered that overexpression of polished rice/tarsal-less (pri/tal) increases the numbers of ES organs as well as SOPs. pri/tal is a polycistronic gene that contains four short open reading frames encoding three 11-amino acid and one 32-amino acid peptides. Ectopic expression of the 11 amino-acid peptides recapitulates the pri/tal misexpression phenotype in ectopic ES organ formation. In situ hybridization experiment reveals that pri/tal mRNA is expressed in the SOPs of the chemosensory organs and the stretch-sensing chordotonal organs.In Drosophila wing development, the Notch signaling pathway mediates the formation of the dorsal-ventral (DV) compartmental boundary and the restriction of the vein width from the primordial veins, the proveins. We also found that pri/tal mRNA is expressed in the DV boundary and the longitudinal proveins, and overexpression of Pri/Tal peptides disrupts the DV boundary formation and helps to expand the width of the wing vein. Genetic analyses further show that a Notch loss-of-function allele strongly enhances these two phenotypes. Cut and E(spl)mβ are target genes of the Notch pathway in DV boundary formation and vein specification, respectively. We also found that overexpression of Pri/Tal peptides abolishes Cut expression and co-expression of Pri/Tal peptides with phyl strongly reduces E(spl)mβ expression. We show for the first time that the overexpression of Pri/Tal 11-amino acid peptides disrupts multiple Notch-mediated processes and reduces Notch target gene expression in Drosophila, suggesting that these peptides have novel antagonistic activity to the Notch pathway. Thus, our discovery might provide insights into designing new therapeutic reagents for Notch-related diseases.
    Journal of Biomedical Science 06/2011; 18(1):42. DOI:10.1186/1423-0127-18-42 · 2.76 Impact Factor
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