CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc

Romero-Pozuelo, Jesús; Demetriades, Constantinos; Schroeder, Phillip; Teleman, Aurelio A.

doi:10.1016/j.devcel.2017.07.019

Cited by 60 publications

(62 citation statements)

References 62 publications

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“…The high coexpression correlation of the 91 translation-related genes suggests an underlying co-regulatory mechanism that remains to be uncovered. Interestingly, in wing imaginal discs, the pS6 staining pattern and TORC activation is patchy and stochastic (Romero-Pozuelo et al, 2017). Likewise, the staining patterns of common proliferation markers such as PH3 + and BrdU + are known to be sporadic and uniformly distributed.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptomic landscapes of pattern formation, proliferation and growth in Drosophila wing imaginal discs

et al. 2019

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Organ formation relies on the orchestration of pattern formation, proliferation and growth during development. How these processes are integrated at the individual cell level remains unclear. In the past decades, studies using Drosophila wing imaginal discs as a model system have provided valuable insights into pattern formation, growth control and regeneration. Here, we provide single cell transcriptomic landscapes of pattern formation, proliferation and growth of wing imaginal discs. We found that patterning information is robustly maintained in the single cell transcriptomic data and can provide reference matrices for computationally mapping single cells into discrete spatial domains. Assignment of wing disc single cells to spatial subregions facilitates examination of patterning refinement processes. We also clustered single cells into different proliferation and growth states and evaluated the correlation between cell proliferation/growth states and spatial patterning. Furthermore, single cell transcriptomic analyses allowed us to quantitatively examine disturbances of differentiation, proliferation and growth in a well-established tumor model. We provide a database to explore these datasets at http:// drosophilayanlab-virtual-wingdisc.ust.hk:3838/v2/. This article has an associated 'The people behind the papers' interview.

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Section: Discussionmentioning

confidence: 99%

Single cell transcriptomic landscapes of pattern formation, proliferation and growth in Drosophila wing imaginal discs

et al. 2019

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“…6). The mechanism(s) of this activation remain to be established, but recent studies in fly imaginal discs point to a possible activation of mTORC1 downstream of CycD/cdk4 and/or E2F1 activation in the cell cycle (Kim et al, 2017; Romero-Pozuelo et al, 2017). In the fly intestine, the mouse trachea, and the mouse muscle, the need for mTORC1 activation to induce stem cell activity contrasts with the requirement for mTORC1 repression to maintain stem cell identity, and as a consequence, repeated episodes of regenerative pressure increase the probability of SC differentiation, resulting in the progressive loss of SCs.…”

Section: Discussionmentioning

confidence: 99%

mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance

et al. 2017

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Summary The balance between self-renewal and differentiation ensures long-term maintenance of stem cell (SC) pools in regenerating epithelial tissues. This balance is challenged during periods of high regenerative pressure and is often compromised in aged animals. Here we show that TOR signaling is a key regulator of SC loss during repeated regenerative episodes. In response to regenerative stimuli, SCs in the intestinal epithelium of the fly and in the tracheal epithelium of mice exhibit transient activation of TOR signaling. Although this activation is required for SCs to rapidly proliferate in response to damage, repeated rounds of damage lead to SC loss. Consistently, age-related SC loss in the mouse trachea and in muscle can be prevented by pharmacologic or genetic inhibition of mTORC1 signaling, respectively. These findings highlight an evolutionarily conserved role of TOR signaling in SC function and identify repeated rounds of mTORC1 activation as a driver of age-related SC decline.

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“…Dissection and immunostaining were performed as described previously [46], adding CaCl 2 1mM during fixation, excepted for Crb staining, which requires a specific fixation [25]. Primary antibodies used are DE-Cad (1/100, DHSB #DCAD2) and N-Cad (1/100 , DHSB, #DN-Ex), Cora (1/200, DHSB, #C615.16), cleaved DCP-1 (1/1000, Cell Signaling, #9578), S6K (1/2000, [47]), pS6K ( 1/400, [48] , pAKT (1/500, Cell signaling, #4054), , dMyc (1/500, SantaCruz BioTechnology #) , Crb (1/50, DHSB, #Cq4), aPKC (1/500, Santa Cruz Biotechnology, #C-20G) , Dlg (1/200, DHSB, #4F3), Dlg5 (1/ 500, this study). Images were taken using a Leica SP5 confocal microscope or a Zeiss 800 Airyscan.…”

Section: Immunostaining and Imagingmentioning

confidence: 99%

Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

Venugopal¹,

Veyssière²,

Couderc³

et al. 2020

Preprint

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Background : Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects. Results : Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent. Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.

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CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc

Cited by 60 publications

References 62 publications

Single cell transcriptomic landscapes of pattern formation, proliferation and growth in Drosophila wing imaginal discs

Single cell transcriptomic landscapes of pattern formation, proliferation and growth in Drosophila wing imaginal discs

mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance

Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

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