Delta activity independent of its activity as a ligand of Notch

Mok, Lee-Peng; Qin, Tielin; Bardot, Boris; LeComte, Matthew D.; Homayouni, Asal; Ahimou, François; Wesley, Cedric S.

doi:10.1186/1471-213x-5-6

Cited by 19 publications

(9 citation statements)

References 52 publications

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“…All the Drosophila cultured cell lines used in this study and details of the procedures used for studying Notch activities have been previously described [8], [9],[12],[16],[19],[26],[35],[54]. Briefly, exponential phase cells growing in fresh medium for two days were used for all cell types and in all experiments the incubation times (after Delta or phorbol ester treatment) were between 15 and 20 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…Specific details of the procedures used are described in our previous publications [2], [5], [6], [8], [12], [16], [19], [26], [35], [54]. The only note we would like to add and emphasize is that the best protein extraction procedure for these experiments is the one that yields molecules closest to their physiological states at the time of extraction: crushing in 1X Laemmli buoffer.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2013

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The Notch gene encodes an evolutionarily conserved cell surface receptor that generates regulatory signals based on interactions between neighboring cells. In Drosophila embryos it is normally expressed at a low level due to strong negative regulation. When this negative regulation is abrogated neurogenesis in the ventral region is suppressed, the development of lateral epidermis is severely disrupted, and the dorsal aminoserosa is expanded. Of these phenotypes only the anti-neurogenic phenotype could be linked to excess canonical Notch signaling. The other phenotypes were linked to high levels of Notch protein expression at the surface of cells in the lateral regions indicating that a non-canonical Notch signaling activity normally functions in these regions. Results of our studies reported here provide evidence. They show that Notch activities are inextricably linked to that of Pkc98E, the homolog of mammalian PKCδ. Notch and Pkc98E up-regulate the levels of the phosphorylated form of IκBCactus, a negative regulator of Toll signaling, and Mothers against dpp (MAD), an effector of Dpp signaling. Our data suggest that in the lateral regions of the Drosophila embryos Notch activity, in conjunction with Pkc98E activity, is used to form the slopes of the opposing gradients of Toll and Dpp signaling that specify cell fates along the dorso-ventral axis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2013

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“…The first, Scabrous (Sca), plays a role in Notch-dependent patterning of eye ommatidia and sensory bristles (Baker et al, 1990; Mlodzik et al, 1990). Sca binds to Notch in trans and activates transcription of the Notch target gene E(spl)C m3 (Mok et al, 2005; Powell et al, 2001). It is not known however, if the effects of Sca require γ-secretase cleavage of Notch, the Notch downstream effector Su(H), or indeed activation of some other signaling pathway.…”

Section: Non-canonical Ligandsmentioning

confidence: 99%

Canonical and Non-Canonical Notch Ligands

D’Souza

Meloty-Kapella

Weinmaster

2010

Current Topics in Developmental Biology

303

274

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Notch signaling induced by canonical Notch ligands is critical for normal embryonic development and tissue homeostasis through the regulation of a variety of cell fate decisions and cellular processes. Activation of Notch signaling is normally tightly controlled by direct interactions with ligand-expressing cells and dysregulated Notch signaling is associated with developmental abnormalities and cancer. While canonical Notch ligands are responsible for the majority of Notch signaling, a diverse group of structurally unrelated non-canonical ligands has also been identified that activate Notch and likely contribute to the pleiotropic effects of Notch signaling. Soluble forms of both canonical and non-canonical ligands have been isolated, some of which block Notch signaling and could serve as natural inhibitors of this pathway. Ligand activity can also be indirectly regulated by other signaling pathways at the level of ligand expression, serving to spatio-temporally compartmentalize Notch signaling activity and integrate Notch signaling into a molecular network that orchestrates developmental events. Here, we review the molecular mechanisms underlying the dual role of Notch ligands as activators and inhibitors of Notch signaling. Additionally, evidence that Notch ligands function independent of Notch are presented. We also discuss how ligand post-translational modification, endocytosis, proteolysis and spatio-temporal expression regulate their signaling activity.

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“…12B). The pre-R8 cell also secretes Sca to enhance Notch activity in response to Delta (Lee et al, 1996; Mok et al, 2005) inducing a conformational change in Notch and the proteolytic cleavage of the Notch intracellular domain (Notch ICD ) (Schroeter et al, 1998; DeStrooper et al, 1999). The Notch ICD translocates into the nucleus and associates with Suppressor of Hairless [Su(H)], converting Su(H) from an inhibitor to a co-transcriptional activator of the Enhancer of Split [ E ( Spl )] gene complex (Artavanis-Tsakonas et al, 1995; Ligoxygakis et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The Drosophila T-box transcription factor Midline functions within the Notch–Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc

Das

Chen

Saucier

et al. 2013

Mechanisms of Development

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We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch–Delta signaling pathway essential for specifying the fates of sensory organ precursor cells. This complements an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in diverse neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch–Delta signaling hierarchy and is essential for maintaining cell viability within by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis.

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Delta activity independent of its activity as a ligand of Notch

Cited by 19 publications

References 52 publications

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

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

Canonical and Non-Canonical Notch Ligands

The Drosophila T-box transcription factor Midline functions within the Notch–Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc

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