LobeandSerrateare required for cell survival during early eye development inDrosophila

Singh, Amit; Xiao, Shi; Choi, Kwang‐Wook

doi:10.1242/dev.02686

Cited by 55 publications

(96 citation statements)

References 79 publications

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“…This renders the mechanism of pc pair selection highly efficient. The implication of the N pathway in the protection of cells from apoptosis or in the induction of apoptosis has already been described in several developmental contexts (Giraldez and Cohen, 2003;Lundell et al, 2003;Orgogozo et al, 2002;Singh et al, 2006). In the process of pc pair selection, the regulation of DIAP1 expression by Notch possibly provides a direct link that merits further exploration.…”

Section: Discussionmentioning

confidence: 91%

A two-step Notch-dependant mechanism controls the selection of the polar cell pair inDrosophilaoogenesis

2010

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SUMMARYOrganisers control the patterning and growth of many tissues and organs. Correctly regulating the size of these organisers is crucial for proper differentiation to occur. Organiser activity in the epithelium of the Drosophila ovarian follicle resides in a pair of cells called polar cells. It is known that these two cells are selected from a cluster of equivalent cells. However, the mechanisms responsible for this selection are still unclear. Here, we present evidence that the selection of the two cells is not random but, by contrast, depends on an atypical two-step Notch-dependant mechanism. We show that this sequential process begins when one cell becomes refractory to Notch activation and is selected as the initial polar cell. This cell then produces a Delta signal that induces a high level of Notch activation in one other cell within the cluster. This Notch activity prevents elimination by apoptosis, allowing its selection as the second polar cell. Therefore, the mechanism used to select precisely two cells from among an equivalence group involves an inductive Delta signal that originates from one cell, itself unable to respond to Notch activation, and results in one other cell being selected to adopt the same fate. Given its properties, this two-step Notch-dependent mechanism represents a novel aspect of Notch action.

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Section: Discussionmentioning

confidence: 91%

A two-step Notch-dependant mechanism controls the selection of the polar cell pair inDrosophilaoogenesis

2010

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“…Thus, the RNAi inhibition is only associated with mutations that condition cell death and is not a secondary consequence of eye morphological changes. The L 2 (Lobe) mutant induces abnormal cell death before the initiation of differentiation (Singh et al 2006) and does not affect w silencing, suggesting the duration of the signal from cell death is temporally limited.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of RNA Interference and Modulation of Transposable Element Expression by Cell Death in Drosophila

2011

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RNA interference (RNAi) regulates gene expression by sequence-specific destruction of RNA. It acts as a defense mechanism against viruses and represses the expression of transposable elements (TEs) and some endogenous genes. We report that mutations and transgene constructs that condition cell death suppress RNA interference in adjacent cells in Drosophila melanogaster. The reversal of RNAi is effective for both the white (w) eye color gene and green fluorescent protein (GFP), indicating the generality of the inhibition. Antiapoptotic transgenes that reverse cell death will also reverse the inhibition of RNAi. Using GFP and a low level of cell death produced by a heat shock-head involution defective (hs-hid) transgene, the inhibition appears to occur by blocking the conversion of double-stranded RNA (dsRNA) to short interfering RNA (siRNA). We also demonstrate that the mus308 gene and endogenous transposable elements, which are both regularly silenced by RNAi, are increased in expression and accompanied by a reduced level of siRNA, when cell death occurs. The finding that chronic ectopic cell death affects RNAi is critical for an understanding of the application of the technique in basic and applied studies. These results also suggest that developmental perturbations, disease states, or environmental insults that cause ectopic cell death would alter transposon and gene expression patterns in the organism by the inhibition of small RNA silencing processes.

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“…PRAS40 phosphorylated at Thr 246 has been detected in mouse cortical neurons after ischemia and reperfusion (43), and the phosphorylation of PRAS40 (Thr 246 ) and the subsequent binding of 14-3-3 are reported to be important for the survival of neuronal cells from apoptosis after ischemic injury in vivo (43,45). Lobe, a putative D. melanogaster ortholog of PRAS40, is required for ventral growth of eye disc and cell survival during early eye development (46,47). Therefore, PRAS40 seems to play an important role in cell survival conserved among different species.…”

Section: Discussionmentioning

confidence: 99%

The Proline-rich Akt Substrate of 40 kDa (PRAS40) Is a Physiological Substrate of Mammalian Target of Rapamycin Complex 1

Oshiro

Takahashi

Yoshino

et al. 2007

Journal of Biological Chemistry

281

301

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The proline-rich Akt substrate of 40 kilodaltons (PRAS40) was identified as a raptor-binding protein that is phosphorylated directly by mammalian target of rapamycin (mTOR) complex 1 (mTORC1) but not mTORC2 in vitro, predominantly at PRAS40 (Ser 183 ). The binding of S6K1 and 4E-BP1 to raptor requires a TOR signaling (TOS) motif, which contains an essential Phe followed by four alternating acidic and small hydrophobic amino acids. PRAS40 binding to raptor was severely inhibited by mutation of PRAS40 (Phe 129 to Ala). Immediately carboxyl-terminal to Phe 129 are two small hydrophobic amino acid followed by two acidic residues. PRAS40 binding to raptor was also abolished by mutation of the major mTORC1 phosphorylation site, Ser 183 , to Asp. PRAS40 (Ser 183 ) was phosphorylated in intact cells; this phosphorylation was inhibited by rapamycin, by 2-deoxyglucose, and by overexpression of the tuberous sclerosis complex heterodimer. PRAS40 (Ser 183 ) phosphorylation was also inhibited reversibly by withdrawal of all or of only the branched chain amino acids; this inhibition was reversed by overexpression of the Rheb GTPase. Overexpressed PRAS40 suppressed the phosphorylation of S6K1 and 4E-BP1 at their rapamycin-sensitive phosphorylation sites, and reciprocally, overexpression of S6K1 or 4E-BP1 suppressed phosphorylation of PRAS40 (Ser 183 ) and its binding to raptor. RNA interference-induced depletion of PRAS40 enhanced the amino acid-stimulated phosphorylation of both S6K1 and 4E-BP1. These results establish PRAS40 as a physiological mTORC1 substrate that contains a variant TOS motif. Moreover, they indicate that the ability of raptor to bind endogenous substrates is limiting for the activity of mTORC1 in vivo and is therefore a potential locus of regulation.The mammalian target of rapamycin (mTOR) 3 is the founding member of the PI-3 kinase-related family of protein (Ser/ Thr) kinases (PIKKs) and controls many important aspects of the cellular response to nutrient sufficiency and growth factors (1). The mTOR polypeptide is now known to function in two distinct, independently regulated hetero-oligomeric complexes, called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Both complexes contain mTOR and the polypeptide mLST8/G␤L; mTORC1 in addition contains raptor (an ortholog of Saccharomyces cerevisiae KOG1), which binds directly to the known mTORC1 substrates S6K1 and 4E-BP1 and is indispensable for their phosphorylation by mTOR in vivo and in vitro. mTORC2 lacks raptor but contains the polypeptides rictor (an ortholog to ScAVO3) and mSin1 (an ortholog of ScAVO1). mTORC2 is one of the activating kinases for Akt, previously called PDK2, and also regulates the actin cytoskeleton through as yet unidentified effectors. Although rapamycin, in complex with FKBP12, binds directly to mTOR in a segment just amino-terminal to the catalytic domain, only mTORC1 binds the FKBP12-rapamycin complex, and thus only mTORC1 is directly susceptible to inhibition by rapamycin.Rapamycin is among the most selective kinase inhibitors k...

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LobeandSerrateare required for cell survival during early eye development inDrosophila

Cited by 55 publications

References 79 publications

A two-step Notch-dependant mechanism controls the selection of the polar cell pair inDrosophilaoogenesis

A two-step Notch-dependant mechanism controls the selection of the polar cell pair inDrosophilaoogenesis

Inhibition of RNA Interference and Modulation of Transposable Element Expression by Cell Death in Drosophila

The Proline-rich Akt Substrate of 40 kDa (PRAS40) Is a Physiological Substrate of Mammalian Target of Rapamycin Complex 1

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