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Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias and lymphomas (T-ALL), making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of(More)
The phyllopod (phyl) gene regulates the fates of a subset of cells in the developing Drosophila eye; in the absence of phyl function, the R1, R6, and R7 photoreceptors are transformed into additional cone cells, whereas ectopic phyl expression in the cone cell precursors transforms these cells into additional R7 cells. Within this group of cells, phyl(More)
T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 genes, which encode crucial components of the Polycomb repressive complex 2 (PRC2), in 25% of T-ALLs. To further(More)
The asense (ase) gene of the achaete-scute complex (AS-C) is expressed in the precursors of all adult sensory organs (SOs), the sensory mother cells (SMCs) and in their immediate progeny. Its deletion causes the loss of some SOs and the abnormal differentiation of part of the remaining ones. These defects, which include malformations of the external part of(More)
The Drosophila eye is patterned by a dorsal-ventral organising centre mechanistically similar to those in the fly wing and the vertebrate limb bud. Here we show how this organising centre in the eye is initiated - the first event in retinal patterning. Early in development the eye primordium is divided into dorsal and ventral compartments. The dorsally(More)
Control of growth determines the size and shape of organs. Localized signals known as 'organizers' and members of the Pax family of proto-oncogenes are both elements in this control. Pax proteins have a conserved DNA-binding paired domain, which is presumed to be essential for their oncogenic activity. We present evidence that the organizing signal Notch(More)
Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginal discs autonomously activate DILP8, a(More)
Activating mutations in NOTCH1 are the most prominent genetic abnormality in T-cell acute Lymphoblastic Leukemia (T-ALL) and inhibition of NOTCH1 signaling with gamma-secretase inhibitors (GSIs) has been proposed as targeted therapy in this disease. However, most T-ALL cell lines with mutations in NOTCH1 fail to respond to GSI therapy. Using gene expression(More)
BACKGROUND During animal development, cells need to make spatially and temporally regulated fate decisions. These decisions are largely controlled by intercellular signalling, often through receptor tyrosine kinases. One of these, the epidermal growth factor receptor (EGFR), regulates multiple cell fate decisions. Its importance in the recruitment of(More)
Neuroepithelial cell proliferation must be carefully balanced with the transition to neuroblast (neural stem cell) to control neurogenesis. Here, we show that loss of the Drosophila microRNA mir-8 (the homolog of vertebrate miR-200 family) results in both excess proliferation and ectopic neuroblast transition. Unexpectedly, mir-8 is expressed in a(More)