The Drosophila IgC2 domain protein friend-of-echinoid, a paralogue of echinoid, limits the number of sensory organ precursors in the wing disc and interacts with the Notch signaling pathway (original) (raw)

Echinoid synergizes with the Notch signaling pathway in Drosophila mesothorax bristle patterning

in proneural clusters. Moreover, combinations of moderate loss-of-function conditions for ed and for different components of the N pathway show clear synergistic interactions manifested as strong neurogenic bristle phenotypes. We conclude that Ed is not essential for, but it facilitates, N signaling. It is known that the N and Egfr pathways act antagonistically in bristle development. Consistently, we find that Ed also antagonizes the bristlepromoting activity of the Egfr pathway, either by the enhancement of N signalling or, similar to the eye, by a more direct action on the Egfr pathway.

Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function

The Journal of cell biology, 1991

The Notch gene in Drosophila encodes a transmembrane protein with homology to EGF that appears to mediate cell-cell interactions necessary for proper epidermal vs. neural fate decisions. In this study, we examine Notch expression in detail throughout embryonic and imaginal development using confocal laser-scanning microscopy and specific mAb probes. We find that Notch is expressed in a tissue-specific manner as early as the cellular blastoderm stage, when cells of the presumptive mesoderm clearly express less Notch than adjacent ectodermal precursors. Notch is abundantly expressed during the initial determination of neuronal lineages, such as the embryonic neuroblasts and the precursors of sensory neurons in the imaginal disc epithelia, but expression quickly decreases during subsequent differentiation. These changing patterns of Notch expression do not correlate well with cell movements, and thus do not appear to support the notion that the major function of Notch is to maintain ep...

Structure and distribution of the Notch protein in developing Drosophila

Genes & Development, 1989

Antibodies to Notch show that it is a stable, high-molecular-weight transmembrane glycoprotein, with epidermal growth factor (EGF)-like elements exposed on the cell surface. The protein is phosphorylated variably on serines of the cytoplasmic domain. Individual Notch polypeptide chains appear to be associated with one another by disulfide bonds, suggesting that homotypic interaction of these proteins is required for function. Immunocytochemistry has revealed striking features of Notch expression that might clarify its function: Cells of the ventral neurogenic ectoderm become conspicuously labeled with the protein prior to embryonic neurogenesis, and Notch appears to be associated with cells destined for both neural and epidermal lineages. High levels of Notch become restricted to neuroblasts as they delaminate from the embryonic ectoderm and are apposed to mesoderm. Mesodermal cells express Notch also, suggesting a possible involvement in neurogenesis, or an unknown role in mesoderm differentiation. In larvae and pupae, a correlation of expression and neuroblast mitotic activity is seen for many cells. Notch produced by a dividing neuroblast may persist on derivative cells, including terminally differentiated neurons and nerve processes. In the larval eye imaginal disk, strong Notch expression appears in the morphogenetic furrow, uniformly on cell surfaces as they cluster to form ommatidia. Expression persists on ommatidia after release from the furrow. These patterns suggest a role for Notch in position-dependent development in both initiation and maintenance of cell-surface interactions. In the eye and embryonic ectoderm, uniform expression on cells interacting to produce different developmental lineages from a single primordium suggests that Notch alone may not be sufficient to elaborate cell fates.

An EP overexpression screen for genetic modifiers of Notch pathway function in Drosophila melanogaster

Genetical Research, 2004

The Notch pathway comprises a signal transduction cascade required for the proper formation of multiple tissues during metazoan development. Originally described in Drosophila for its role in nervous system formation, the pathway has attracted much wider interest owing to its fundamental roles in a range of developmental and disease-related processes. Despite extensive analysis, Notch signaling is not completely understood and it appears that additional components of the pathway remain to be identified and characterized. Here, we describe a novel genetic strategy to screen for additional Notch pathway genes. The strategy combines partial loss of function for pathway activity with Enhancer-promoter (EP)-induced overexpression of random loci across the dorsoventral wing margin. Mastermind (Mam) is a nuclear component of the Notch signaling cascade. Using a GAL4-UAS-driven dominant-negative form of Mam, we created a genotype that exhibits a completely penetrant dominant wing-nicking ph...

Wing vein formation in Drosophila melanogaster: Hairless is involved in the cross-talk between Notch and EGF signaling pathways

Mechanisms of Development, 2002

Drosophila is controlled by different morphogenetic pathways, including Notch. Hairless (H) antagonizes Notch target gene activation by binding to the Notch signal transducer Suppressor of Hairless [Su(H)]. Accordingly, overexpression of H phenocopies reduction of Notch activity. Deletion of the Su(H)-binding domain in H-C2 results in loss of H activity. However, overexpression of H-C2 induces formation of ectopic veins. In a screen for genetic modifiers of this phenotype, we have identified several genes involved in Notch and epidermal growth factor (EGF) signaling. Most notably veinlet, an activator of EGF signaling, acts downstream of H-C2. H-C2 positively regulates veinlet maybe through inhibition of inter-vein determinants in agreement with a model, whereby Notch and EGF signaling pathways cross-regulate vein pre-patterning. q

echinoidmutants exhibit neurogenic phenotypes and show synergistic interactions with the Notch signaling pathway

Development, 2003

During neurogenesis in Drosophila, groups of ectodermal cells are endowed with the capacity to become neuronal precursors. The Notch signaling pathway is required to limit the neuronal potential to a single cell within each group. Loss of genes of the Notch signaling pathway results in a neurogenic phenotype: hyperplasia of the nervous system accompanied by a parallel loss of epidermis. Echinoid (Ed), a cell membrane associated Immunoglobulin C2-type protein, has previously been shown to be a negative regulator of the EGFR pathway during eye and wing vein development. Using in situ hybridization and antibody staining of whole-mount embryos, we show that Ed has a dynamic expression pattern during embryogenesis. Embryonic lethal alleles of ed reveal a role of Ed in restricting neurogenic potential during embryonic neurogenesis, and result in a phenotype similar to that of loss-of-function mutations of Notch signaling pathway genes. In this process Ed interacts closely with the Notch s...

The Murine Ortholog of Notchless, a Direct Regulator of the Notch Pathway in Drosophila melanogaster, Is Essential for Survival of Inner Cell Mass Cells

Molecular and Cellular Biology, 2006

Notch signaling is an evolutionarily conserved pathway involved in intercellular communication and is essential for proper cell fate choices. Numerous genes participate in the modulation of the Notch signaling pathway activity. Among them, Notchless (Nle) is a direct regulator of the Notch activity identified in Drosophila melanogaster. Here, we characterized the murine ortholog of Nle and demonstrated that it has conserved the ability to modulate Notch signaling. We also generated mice deficient for mouse Nle (mNle) and showed that its disruption resulted in embryonic lethality shortly after implantation. In late mNle −/− blastocysts, inner cell mass (ICM) cells died through a caspase 3-dependent apoptotic process. Most deficient embryos exhibited a delay in the temporal down-regulation of Oct4 expression in the trophectoderm (TE). However, mNle-deficient TE was able to induce decidual swelling in vivo and properly differentiated in vitro. Hence, our results indicate that mNle is m...

The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis

Genes & Development, 1990

The genetic and molecular analysis of the Notch locus, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, suggests that the Notch protein is involved in a cell interaction mechanism essential for the differentiation of the embryonic nervous system of Drosophila. Taking advantage of the negative complementation between two Notch mutations that affect the extracellular domain of the protein, we have tried to dissect the genetic circuitry in which Notch is integrated by searching for genes whose products may interact with the Notch protein. This genetic screen has led to the identification of a surprisingly restricted set of interacting loci, including Delta and mastermind. Like Notch, both of these genes belong to a group of loci, the neurogenic loci, which have been previously identified by virtue of their similar mutant phenotype affecting early neurogenesis. We extend these studies by systematically exploring interactions between sp...