Notch and PKC Are Involved in Formation of the Lateral Region of the Dorso-Ventral Axis in Drosophila Embryos

Tremmel, Daniel M.; Resad, Sedat; Little, Christopher J.; Wesley, Cedric S.

doi:10.1371/journal.pone.0067789

Cited by 15 publications

(18 citation statements)

References 103 publications

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“…It is possible that the regulation of zen and other responsive genes is mediated through Notch signaling. Both canonical Notch signaling in the nucleus and the non-canonical Notch signaling are up-regulated in heph 03429 embryos [22], [30]. The canonical Notch signaling involves ligand-dependent processing, release, and translocation into the nucleus of the Notch intracellular domain (N intra /NICD) to activate target genes [31]–[33].…”

Section: Discussionmentioning

confidence: 99%

Drosophila Polypyrimidine Tract-Binding Protein (DmPTB) Regulates Dorso-Ventral Patterning Genes in Embryos

et al. 2014

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The Drosophila polypyrimidine tract-binding protein (dmPTB or hephaestus) plays an important role during embryogenesis. A loss of function mutation, heph03429, results in varied defects in embryonic developmental processes, leading to embryonic lethality. However, the suite of molecular functions that are disrupted in the mutant remains unknown. We have used an unbiased high throughput sequencing approach to identify transcripts that are misregulated in this mutant. Misregulated transcripts show evidence of significantly altered patterns of splicing (exon skipping, 5′ and 3′ splice site switching), alternative 5′ ends, and mRNA level changes (up and down regulation). These findings are independently supported by reverse-transcription-polymerase chain reaction (RT-PCR) analysis and in situ hybridization. We show that a group of genes, such as Zerknüllt, z600 and screw are among the most upregulated in the mutant and have been functionally linked to dorso-ventral patterning and/or dorsal closure processes. Thus, loss of dmPTB function results in specific misregulated transcripts, including those that provide the missing link between the loss of dmPTB function and observed developmental defects in embryogenesis. This study provides the first comprehensive repertoire of genes affected in vivo in the heph mutant in Drosophila and offers insight into the role of dmPTB during embryonic development.

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Section: Discussionmentioning

confidence: 99%

Drosophila Polypyrimidine Tract-Binding Protein (DmPTB) Regulates Dorso-Ventral Patterning Genes in Embryos

et al. 2014

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“…Our parallel studies in embryogenesis showed that N nd1 and N nd3 embryos manifest high levels of a noncanonical Notch signaling activity at the cell surface that is based on Pkc98E activity (Tremmel et al, 2013). Therefore, we examined whether PKC98E activity is involved in the upregulation of hyper-PO4 CREB.…”

Section: Pkc98e Regulates Hyper-po4 Creb Level and Ltm Formationmentioning

confidence: 99%

“…Our recent studies in Drosophila embryos have identified a Notch activity that is located at the cell surface and involves the activity of Pkc98E, the Drosophila homolog of the novel class of PKC. This Notch-PKC activity is specific to the lateral regions of the embryo and upregulates the levels of F-actin and the phosphorylated form of Cactus, the Drosophila homolog of IB that is a negative regulator of Toll/NFB pathway (Wesley et al, 2011;Tremmel et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Notch-Inducible Hyperphosphorylated CREB and Its Ultradian Oscillation in Long-Term Memory Formation

Zhang¹,

Little²,

Tremmel³

et al. 2013

Journal of Neuroscience

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Notch is a cell surface receptor that is known to regulate developmental processes by establishing physical contact between neighboring cells. Many recent studies show that it also plays an important role in the formation of long-term memory (LTM) in adults, implying that memory formation requires regulation at the level of cell-cell contacts among brain cells. Neither the target of Notch activity in LTM formation nor the underlying mechanism of regulation is known. We report here results of our studies in adult Drosophila melanogaster showing that Notch regulates dCrebB-17A, the CREB protein. CREB is a transcriptional factor that is pivotal for intrinsic and synaptic plasticity involved in LTM formation. Notch in conjunction with PKC activity upregulates the level of a hyperphosphorylated form of CREB (hyper-PO4 CREB) and triggers its ultradian oscillation, both of which are linked to LTM formation. One of the sites that is phosphorylated in hyper-PO4 CREB is serine 231, which is the functional equivalent of mammalian CREB serine 133, the phosphorylation of which is an important regulator of CREB functions. Our data suggest the model that Notch and PKC activities generate a cyclical accumulation of cytoplasmic hyper-PO4 CREB that is a precursor for generating the nuclear CREB isoforms. Cyclical accumulation of CREB might be important for repetitive aspects of LTM formation, such as memory consolidation. Because Notch, PKC, and CREB have been implicated in many neurodegenerative diseases (e.g., Alzheimer's disease), our data might also shed some light on memory loss and dementia.

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“…The newly discovered non-canonical Notch activity was found to up-regulate the level of F-actin and promote the formation of the longitudinal F-actin cables during dorsal closure ( Wesley et al, 2011 ). During dorso-ventral axis formation, it was found to up-regulate the level of a phosphorylated form of Cactus, the Drosophila homolog of IκB, that is a negative regulator of Toll/Dorsal (NFκB) signaling ( Tremmel et al, 2013 ).…”

Section: Non-canonical Notch Signaling Mechanisms In D Rosomentioning

confidence: 99%

From Drosophila development to adult: clues to Notch function in long-term memory

Zhang

Yin

Wesley

2013

Front. Cell. Neurosci.

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Notch is a cell surface receptor that is well known to mediate inter-cellular communication during animal development. Data in the field indicate that it is also involved in the formation of long-term memory (LTM) in the fully developed adults and in memory loss upon neurodegeneration. Our studies in the model organism Drosophila reveal that a non-canonical Notch-protein kinase C activity that plays critical roles in embryonic development also regulates cyclic-AMP response element binding protein during LTM formation in adults. Here we present a perspective on how the various known features of Notch function relate to LTM formation and how they might interface with elements of Wingless/Wnt signaling in this process.

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Notch and PKC Are Involved in Formation of the Lateral Region of the Dorso-Ventral Axis in Drosophila Embryos

Cited by 15 publications

References 103 publications

Drosophila Polypyrimidine Tract-Binding Protein (DmPTB) Regulates Dorso-Ventral Patterning Genes in Embryos

Drosophila Polypyrimidine Tract-Binding Protein (DmPTB) Regulates Dorso-Ventral Patterning Genes in Embryos

Notch-Inducible Hyperphosphorylated CREB and Its Ultradian Oscillation in Long-Term Memory Formation

From Drosophila development to adult: clues to Notch function in long-term memory

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