bioRxiv Science⌕ Search

Biology subjects

Hauert, B.

Publications and source records attributed to Hauert, B..

4 recordsLinked to original sources

Temporal Dynamics of Azot Expression Following Traumatic Brain Injury.

Cell competition, a conserved biological process in which cells compete for survival based on relative fitness, has emerged as a critical mechanism in diverse biological contexts. Here, we investigate the role of cell competition in traumatic brain injury (TBI) by characterizing the temporal expression pattern of Azot, a key downstream effector of fitness-based selection, following injury in Drosophila melanogaster. Our findings reveal a distinct temporal profile of Azot expression post-TBI, with TUNEL assays confirming that Azot-expressing cells undergo apoptotic elimination. We demonstrate that following injury, the proportion of dying cells marked as "losers" significantly increases compared to non-injured conditions, indicating that cell competition becomes a predominant elimination mechanism during acute post-injury phases. Contrary to previous findings in neurodegenerative disease models where competition was restricted to neurons, we show that following TBI, both neurons and glia are subject to competitive elimination. Furthermore, in azot knockout conditions, we observe an accumulation of cells attempting to express Azot, suggesting impaired clearance of suboptimal cells. These findings advance our understanding of cellular quality control mechanisms following brain injury and may inform the development of novel therapeutic approaches to enhance functional recovery after TBI.

cell biology↗

Characterising the Modulatory Role of Ikebana in Flower-Dependent Cell Competition

Tissues encompass a quality control mechanism that promotes their optimal state. This mechanism, designated cell competition, is characterised by the elimination of suboptimal yet viable cells when they are near healthier cells within the same tissue compartment. This study explores Flower-dependent cell competition and introduces Ikebana as a novel player. The differential expression of the flower isoforms labels cells as winners or losers, influencing their fate in diverse contexts, including eye development, traumatic brain injury, and Alzheimers disease. Ikebana, ubiquitously produced in wing imaginal discs and adult brains, modulates loser cell elimination. Reduction of ikebana expression correlates with an increased number of loser cells, while its overexpression in the Alzheimers disease model reduces the number of Flower LoseB-positive cells. We suggest that Ikebana protects loser cell elimination, particularly when excessive elimination of loser cells can compromise tissue function. Thus, Ikebana might be a potential therapeutic target for modulating Flower LoseB expression.

cell biology↗

Longitudinal analysis of Flower-dependent cell competition fitness markers in Drosophila melanogaster

Cell competition is a conserved phenomenon spanning from arthropods to humans. It involves the elimination of viable yet suboptimal "loser" cells when juxtaposed with their fitter "winner" counterparts. This process has received increased attention for its implications in cancer initiation and progression, neurodegeneration, and ageing. This study investigates the presence of the loser fitness fingerprint Flower LoseB (Fwe LB) and the fitness checkpoint Azot in the optic lobes over a period of 28 days. Notably, the absence of Azot is conventionally linked to the accumulation of loser cells over time. However, our investigation reveals that this accumulation is not perpetual and, intriguingly, Azot is not required for loser cell elimination in this context. Furthermore, we estimate that fewer than 50% of Fwe LB-expressing cells also express Azot and undergo apoptosis. Remarkably, our calculations also demonstrate that over 50% of cells undergoing apoptosis at any given time point are positive for the loser markers Fwe LB and Azot. This comprehensive analysis of fitness marker dynamics over a 28-day timeframe sheds new light on the intricate mechanisms governing Flower-dependent cell competition.

cell biology↗

Culling less fit neurons protects against amyloid-β induced brain damage and cognitive and motor decline

Alzheimers disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secreted form of human amyloid-{beta}42 peptide and show that it recapitulates key aspects of AD pathology, including neuronal death and impaired long-term memory. We found that neuronal apoptosis is mediated by cell fitness-driven neuronal culling, which selectively eliminates impaired neurons from brain circuits. We show that removal of less fit neurons delays amyloid-{beta}42-induced brain damage and protects against cognitive and motor decline, suggesting that - contrary to common knowledge - neuronal death may have a beneficial effect in AD.

developmental biology↗