- An activity of Notch regulates JNK signalling and affects dorsal closure in Drosophila
Current Biology, Volume 9, Issue 9, 6 May 1999, Pages 460-469
Vincent Zecchini, Keith Brennan and Alfonso Martinez-Arias
SummaryBackground: The Drosophila Notch protein is a receptor that controls cell fate during embryonic development, particularly in lateral inhibition, a process that acts on groups of cells that share a particular developmental potential to restrict the number of cells that will adopt that cell fate. The process of lateral inhibition is implemented by the nuclear protein Suppressor of Hairless (Su(H)) and is triggered by the ligand Delta. Recent results have shown that the interaction between Delta and Notch triggers the cleavage of the intracellular domain of Notch which then translocates to the nucleus and binds to Su(H).Results: We find that Notch plays a role in the patterning of the dorsal epidermis of the Drosophila embryo and that this function of Notch is independent of Su(H), requires Notch at the plasma membrane and targets the c-Jun N-terminal kinase (JNK) signalling pathway. Notch mutants show high levels of JNK activity and can rescue the effects of lowered JNK signalling resulting from mutations in the hemipterous and basket genes. Two regions of the intracellular domain of Notch are involved: the Cdc10/ankyrin repeats, which downregulate signalling through the JNK pathway, and a region carboxy-terminal to these repeats, which regulates this negative function.Conclusions: Our results reveal a novel signalling activity of Notch that does not require its cleavage and acts by modulating signalling through the JNK pathway. In the Drosophila embryo, this activity plays an important role in the morphogenetic movements that drive dorsal closure.
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- Proneural function of neurogenic genes in the developing Drosophila eye
Current Biology, Volume 7, Issue 2, 1 February 1997, Pages 122-132
Nicholas E. Baker and Sung-Yun Yu
SummaryBackground: Intercellular signals are major determinants of cell fate during development. Certain signals and receptors are important for many different cell-fate decisions, suggesting that cellular responses to similar signals change during development. Few transitions between such distinct cellular responses have been studied. The Drosophila genes Notch and hedgehog function during intracellular signaling at various stages of development. In the specific case of development of the Drosophila eye, expression of the proneural gene atonal is induced in response to Hedgehog signaling and then becomes subject to autoregulation. The receptor protein Notch has previously been reported to function in the selection of single founder photoreceptor cells (R8 cells) by inhibiting atonal expression. On this basis, complete elimination of Notch gene function would be expected to cause neural hyperplasia in the eye.Results: Contrary to expectation, we detect a reduction in neural differentiation both in cells expressing a conditional Notch allele and in those lacking expression of either Notch or its ligand Delta. We show here that Notch signaling acts after the initial Hedgehog-driven expression of atonal to enhance proneural competence of the atonal-expressing cells and also to terminate their response to the Hedgehog signals. This occurs before the Notch-induced lateral inhibition of atonal expression within the same cells.Conclusion: Notch has sequentially opposite effects on the same cells, by first promoting and then inhibiting proneural gene function. This apparently paradoxical sequence of events has two possible consequences. Firstly, coupling of alternative cellular responses to the same receptor may prevent them from occurring simultaneously. Secondly, consecutive regulatory processes become temporally coupled, so that these events follow on from each other, without gaps or overlaps.
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- Control of Daughter Cell Fates during Asymmetric Division: Interaction of Numb and Notch
Neuron, Volume 17, Issue 1, 1 July 1996, Pages 27-41
Ming Guo, Lily Yeh Jan and Yuh Nung Jan
SummaryDuring development of the Drosophila peripheral nervous system, a sensory organ precursor (SOP) cell undergoes rounds of asymmetric divisions to generate four distinct cells of a sensory organ. Numb, a membrane-associated protein, is asymmetrically segregated into one daughter cell during SOP division and acts as an inherited determinant of cell fate. Here, we show that Notch, a transmembrane receptor mediating cell–cell communication, functions as a binary switch in cell fate specification during asymmetric divisions of the SOP and its daughter cells in embryogenesis. Moreovernumb negatively regulates Notch, probably through direct protein–protein interaction that requires the phosphotyrosine-binding (PTB) domain of Numb and either the RAM23 region or the very C-terminal end of Notch. Notch then positively regulates a transcription factor encoded bytramtrack (ttk). This leads to Ttk expression in the daughter cell that does not inherit Numb. Thus, the inherited determinant Numb bestows a bias in the machinery for cell–cell communication to allow the specification of distinct daughter cell fates.
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Copyright © 1987 All rights reserved.
Cell, Volume 51, Issue 4, 539-548, 20 November 1987
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Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus★ Present address, Department of Biochemistry and Biophysics, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153.
† On sabbatical leave from Department of Biochemistry, Louisiana State University, Baton Rouge, Louisiana 70803.
- The Drosophila neurogenic protein Notch is largely composed of tandemly repeated copies of an epidermal growth factor-like sequence. Notch protein contains 36 EGF-like elements, but no two are identical. In the present study, eight mutations are correlated with single amino acid substitutions in EGF-homologous elements of this protein. Genetic analyses of the mutations and comparisons of DNA from mutant and wild-type flies indicate that differentiation of function exists among the tandemly repeated EGF-like sequences and that the total number of repeats and minor variations from the consensus repeat sequence are important for wild-type Notch protein function. One group of EGF-like repeats may be involved in the formation of functional Notch dimers or multimeric proteins. EGF-like elements in a second region of the Notch protein appear to govern its interaction with the product of Enhancer of split, another neurogenic locus of D. melanogaster.