Control of differentiation and cell cycling in leaf development

[EN]Leaf development is characterised by a period of mitotic cycles which control the cell number in the developing organ followed by cell expansion and an associated switch to endocycles. D-type cyclin (CYCD) activity plays an important role in determining the timing of this switch during leaf development. Leaf development also requires the down-regulation of meristem markers such as SHOOTMERISTEMLESS (STM), whose continued expression promotes the maintenance of an undifferentiated state and continued mitotic cycles. Cytokinin appears to be closely involved in determining the mitotic state acting both downstream of STM and upstream of CYCD activity and the interplay of these factors with cell cycle control and the transition from mitotic cycles to endocycles will be discusse

Lineage- and stage-specific expressed CYCD7;1 coordinates the single symmetric division that creates stomatal guard cells

Plants, with cells fixed in place by rigid walls, often utilize spatial and temporally distinct cell division programs to organize and maintain organs. This leads to the question of how developmental regulators interact with the cell cycle machinery to link cell division events with particular developmental trajectories. In Arabidopsis leaves, the development of stomata, two-celled epidermal valves that mediate plant-atmosphere gas exchange, relies on a series of oriented stem cell-like asymmetric divisions followed by a single symmetric division. The stomatal lineage is embedded in a tissue in which other cells transition from proliferation to postmitotic differentiation earlier, necessitating stomatal lineage-specific factors to prolong competence to divide. We show that the D-type cyclin, CYCD7;1, is specifically expressed just prior to the symmetric guard cell-forming division, and that it is limiting for this division. Further, we find that CYCD7;1 is capable of promoting divisions in multiple contexts, likely through RBR1-dependent promotion of the G1/S transition, but that CYCD7;1 is regulated at the transcriptional level by cell type-specific transcription factors that confine its expression to the appropriate developmental windo

Evaluation of a novel liquid biopsy-based ColoScape assay for mutational analysis of colorectal neoplasia and triage of FIT+ patients: a pilot study

Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study. The assay was evaluated on 52 prospectively collected whole-blood samples obtained from FIT+ patients enrolled in the CRC screening programme of ASL NAPOLI 3 SUD, using colonoscopy as confirmation. The assay's sensitivity for advanced adenomas was 53.8% and the specificity was 92.3%. The PPV was 70.0% and negative predicitive value (NPV) was 85.7%. Workflow optimisation is essential to maximise sensitivity. Of note, four of the six positive cases missed by ColoScape had a less than suboptimal DNA input (data not shown). Had they been ruled out as inadequate, sensitivity would have increased from 53.8% to 69%. However, as stated previously, this is not a clinical trial, but rather an initial, preliminary technical evaluation. In conclusion this study shows that ColoScape is a promising tool and further studies are warranted in order to validate its use for the triage of FIT+ patients