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Biology subjects

Aerne, B. L.

Publications and source records attributed to Aerne, B. L..

3 recordsLinked to original sources

Growth compensation upon changes in tissue size in the Drosophila abdomen

Attaining the appropriate size during development is essential for the function of animal tissues and organs. Robust tissue size control implies the existence of compensatory mechanisms that allow developing systems to recover from growth perturbations. However, the difficulty of directly observing normal or compensatory developmental growth means we have little understanding of the cellular behaviours that confer robustness to tissue size control. Here, we study how growth perturbations affect proliferation kinetics and the timing of growth termination of Drosophila histoblasts, the progenitors that give rise to the adult abdominal epidermis. Histoblasts undergo extensive growth and proliferation during the pupal stage, which is accessible for long-term live-imaging and precise quantitative analysis. By manipulating cell number or volume prior to the pupal growth phase, we changed the starting size of the abdomen primordium, then observed how the histoblasts adapted to these changes by altering their growth dynamics. We show that, upon a decrease in starting tissue size, the histoblasts compensate by extending their temporal proliferative window, undergoing additional cell cycles, as well as increasing their apical area to maximise coverage of the abdominal surface. When initial tissue size is increased, the histoblasts undergo fewer division cycles and arrest proliferation earlier than normal. Thus, the proliferative window of this tissue is flexible enough to buffer for changes in tissue size. Our data also suggest that the histoblasts sense both spatial and temporal cues to arrest their growth at the appropriate time and ensure accurate tissue size control.

developmental biology↗

Meru co-ordinates spindle orientation with cell polarity and cell cycle progression

Correct mitotic spindle alignment is essential for tissue architecture and plays an important role in cell fate specification through asymmetric cell division. Spindle tethering factors such as Drosophila Mud (NuMA in mammals) are recruited to the cell cortex and capture astral microtubules, pulling the spindle in the correct orientation. However, how spindle tethering complexes read the cell polarity axis and how spindle attachment is coupled to mitotic progression remains poorly understood. We explore these questions in Drosophila sensory organ precursors (SOPs), which divide asymmetrically to give rise to the epidermal mechanosensory bristles. We show that the scaffold protein Meru, which is recruited to the posterior cortex by the Frizzled/Dishevelled planar cell polarity complex, in turn recruits Mud, linking the spindle tethering and polarity machineries. Furthermore, Cyclin A/Cdk1 associates with Meru at the posterior cortex, promoting the formation of the Mud/Meru/Dsh complex via Meru and Dsh phosphorylation. Thus, Meru couples spindle orientation with cell polarity and provides a cell cycle-dependent cue for spindle tethering.

developmental biology↗

The ecdysone receptor promotes or suppresses proliferation according toligand level

Steroid hormones control various cellular activities in a context-dependent manner. For example, ecdysone, which acts through a type II nuclear receptor, has seemingly opposite effects in Drosophila wing precursors, promoting proliferation during larval stages, and triggering proliferation arrest at pupariation. We find that wing precursors proliferate normally in the complete absence of the ecdysone receptor (EcR), whether ecdysone is present or not, suggesting that ecdysone overrides a default antiproliferative activity of the receptor. By contrast, termination of proliferation by high concentration of 20E at the end of larval life involves conventional gene regulation by the ligand-receptor complex. The switch from one mode of regulation to the other is determined by ligand level, as measured with a calibrated EcR transcriptional reporter and ex vivo proliferation assays. Accordingly, RNA Seq analysis uncovers distinct transcriptional responses to different doses of ecdysone. Some genes are only activated at high doses (high threshold targets) and likely to comprise genes that stop proliferation at pupariation, when ecdysone titres are high. We find that other target genes respond to all physiological concentrations of ecdysone. Some of these genes are known to promote proliferation and could therefore contribute to the pro-proliferation activity of low-level ecdysone. Finally, we show mathematically and with synthetic reporters that relatively simple combinations of regulatory elements can recapitulate the behaviour of both types of target genes.

developmental biology↗