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- Arefin, Md Badrul, et al.
(författare)
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Drosophila Neuroblast Selection Is Gated by Notch, Snail, SoxB, and EMT Gene Interplay
- 2019
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Ingår i: Cell Reports. - Cambridge, United States : CELL PRESS. - 2211-1247. ; 29:11, s. 3636-3651.e3
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Tidskriftsartikel (refereegranskat)abstract
- In the developing Drosophila central nervous system (CNS), neural progenitor (neuroblast [NB]) selection is gated by lateral inhibition, controlled by Notch signaling and proneural genes. However, proneural mutants still generate many NBs, indicating the existence of additional proneural genes. Moreover, recent studies reveal involvement of key epithelial-mesenchymal transition (EMT) genes in NB selection, but the regulatory interplay between Notch signaling and the EMT machinery is unclear. We find that SoxNeuro (SoxB family) and worniu (Snail family) are integrated with the Notch pathway, and constitute the missing proneural genes. Notch signaling, the proneural, SoxNeuro, and worniu genes regulate key EMT genes to orchestrate the NB selection process. Hence, we uncover an expanded lateral inhibition network for NB selection and demonstrate its link to key players in the EMT machinery. The evolutionary conservation of the genes involved suggests that the Notch-SoxB-Snail-EMT network may control neural progenitor selection in many other systems.
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| 2. |
- Bivik Stadler, Caroline, 1986-, et al.
(författare)
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PIP degron-stabilized Dacapo/p21(Cip)(1) and mutations in ago act in an anti- versus pro-proliferative manner, yet both trigger an increase in Cyclin E levels
- 2019
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Ingår i: Development. - : COMPANY BIOLOGISTS LTD. - 0950-1991 .- 1477-9129. ; 146:13
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Tidskriftsartikel (refereegranskat)abstract
- During cell cycle progression, the activity of the CycE-Cdk2 complex gates S-phase entry. CycE-Cdk2 is inhibited by CDK inhibitors (CKIs) of the Cip/Kip family, which include the human p21(Cip)(1) and Drosophila Dacapo (Dap) proteins. Both the CycE and Cip/Kip family proteins are under elaborate control via protein degradation, mediated by the Cullin-RING ligase (CRL) family of ubiquitin ligase complexes. The CRL complex SCFFoxw7/Ago targets phosphorylated CycE, whereas p21(Cip)(1) and Dap are targeted by the CRLCdf2 complex, binding to the PIP degron. The role of CRL-mediated degradation of CycE and Cip/Kip proteins during CNS development is not well understood. Here, we analyse the role of ago (Fbxw7)-mediated CycE degradation, and of Dap and p21(Cip)(1) degradation during Drosophila CNS development. We find that ago mutants display over-proliferation, accompanied by elevated CycE expression levels. By contrast, expression of PIP degron mutant Dap and p21(Cip)(1) transgenes inhibit proliferation. However, surprisingly, this is also accompanied by elevated CycE levels. Hence, ago mutation and PIP degron Cip/Kip transgenic expression trigger opposite effects on proliferation, but similar effects on CycE levels.
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| 3. |
- Skoglund, Karin, 1980-, et al.
(författare)
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Colon data from the Visual Sweden project DROID
- 2019
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Annan publikationabstract
- The dataset consists of 101 H&E-stained colon whole slide images (WSI) - 52 abnormal and 49 benign cases. All significant abnormal findings identified are outlined and categorized into 15 types such as hyperplastic polyp, high grade adenocarcinoma and necrosis. Other tissue components such as mucosa, submucosa, as well as the surgical margin are delineated to create a complete histological map. In total, 756 separate annotations have been made to segment the different tissue structures and link them to ontological information.
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