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Dalle Nogare, D.

Publications and source records attributed to Dalle Nogare, D..

6 recordsLinked to original sources

AI4Life Open Calls and Public Challenges: why, how, and what we have learned.

Within AI4Life, we ran three Open Calls and three Public Challenges (2023-2025), supporting 22 bioimage analysis projects from 151 applications and engaging 225 challenge participants, with the aim of applying FAIR deep learning in the life sciences. Our experience offers a view of the current state of bioimage analysis, the landscape of available tools, as well as the existing gaps between method developers, tool producers and potential users. It highlights that even after careful selection for AI-ready projects, most still require substantial effort to apply deep learning, and that the field still relies heavily on established, well-rounded methods to solve common problems. We come to the conclusion that for scientific AI in biology, the rate-limiting step is not methods and models but data, annotations, and shared infrastructure underneath them.

bioinformatics↗

Signaling and Mechanics influence the number and size of epithelial rosettes in the migrating zebrafish Posterior Lateral Line primordium

A prepattern of Fgf signaling triggers formation of epithelial rosettes as protoneuromasts form periodically in the migrating Posterior Lateral Line primordium. However, the number and size of epithelial rosettes is influenced by the balance of mechanical interactions that promote or oppose their formation. Selective slowing of leading cells in the primordium can result in the fusion of two rosettes to form one larger one, while slowing of trailing cells can result in splitting of a previously formed rosette to form two smaller ones. These observations can be accounted for by mechanics-based models, where local interactions associated with apical constriction and cell adhesion promote formation of rosettes, while tension along the length of the primordium, influenced by the relative efficacy of leading and trailing cell migration, opposes their formation. We describe computational models that illustrate how the relative speed of leading versus trailing cells, as well as changes in cell adhesion and mechanical coupling, can influence the pattern of protoneuromast formation and deposition by the migrating primordium. Our studies illustrate how signaling and mechanics together influence morphogenesis in the migrating primordium.

developmental biology↗

FeatureForest: the power of foundation models, theusability of random forests

Once the work at the microscope is done, biological discoveries rely heavily on proper downstream analysis. This often amounts to first segmenting the biological objects of interest in the image before performing a quantitative analysis. Deep-learning (DL) is nowadays ubiquitous in such segmentation tasks. However, DL can be cumbersome to apply, as it often requires large amount of manual labeling to produce ground-truth data, and expert knowledge to train the models from scratch. Nonetheless, the performance of large foundation models, although trained on natural images, are improving on scientific images with every new model released. They, however, require either manual prompting or tedious post-processing to selectively segment the biological objects of interest. Classical machine learning algorithms, such as random forest classifiers, on the other hand, are well-established, easy to train, and often yield results of sufficient quality for downstream processing tasks, hence their continued popularity. Unfortunately, they are limited to objects with distinct, well-defined textures compared to their environment. This generally limits their usefulness to structures easy to recognize. Here, we present FeatureForest, an open-source tool that leverages the feature embeddings of large foundation models to train a random forest classifier, thereby providing users with a rapid way of semantically segmenting complex images using only a few labeling strokes. We demonstrate the improvement in performance over a variety of datasets, including large and complex volumetric electron microscopy stacks. Our implementation is available in napari, currently integrates four foundation models, and can easily be extended to any new model once they become available.

bioinformatics↗

Local DNA compaction creates TF-DNA clusters that enable transcription

Transcription factor (TF) clusters have been suggested to facilitate transcription. The mechanisms driving the formation of TF clusters and their impact on transcription, however, remain largely unclear. This is mostly due to the lack of a tractable system. Here, we exploit the transcriptional activation of mir430 in zebrafish embryos to simultaneously follow the dynamic formation of a large Nanog cluster, the underlying DNA, and transcription output by live imaging at high temporal and spatial resolution. We find that the formation of a Nanog cluster that can support transcription requires local DNA compaction. This brings more Nanog-binding sites into the cluster, and therefore more Nanog. Importantly, we find that Nanog stabilizes this TF-DNA cluster, which emphasizes the interdependent relationship between TFs and DNA dynamics in cluster formation. Once the Nanog-DNA cluster at the mir430 locus reaches a maximum amount of Nanog, transcription begins. This maximum is a locus-intrinsic feature, which shows that the locus self-regulates the recruitment of an optimal amount of Nanog. Our study supports a model in which endogenous TF clusters positively impact transcription and form through a combination of DNA binding and local DNA compaction.

cell biology↗

A metabolic shift to glycolysis promotes zebrafish tail regeneration through TGF-β dependent dedifferentiation of notochord cells to form the blastema

Mammals are generally poor at tissue regeneration, in contrast, fish maintain a high capacity for regenerating complex tissues after injury. Using larval zebrafish, we show that tail amputation triggers an metabolic shift to glycolysis in cells surrounding the notochord as they reposition to the amputation site. Blocking glycolysis prevents the fin from regenerating after amputation due to the failure to form a normal, pluripotent blastema. We performed a time series of scRNA-sequencing on regenerating tails under normal conditions or in the absence of glycolysis. Strikingly, we detected a transient cell population in the single cell analysis that represents notochord sheath cells undergoing a TGF-{beta} dependent dedifferentiation and epithelium-to-mesenchyme transition to become pluripotent blastema cells. We further demonstrated that the metabolic switch to glycolysis is required for TGF-{beta} signaling and blocking either glycolysis or TGF-{beta} receptors results in aberrant blastema formation through the suppression of essential EMT mediators such as snai1.

developmental biology↗

A sheath of motile cells supports collective migration of the Zebrafish posterior lateral line primordium under the skin

During embryonic development, cells must navigate through diverse three-dimensional environments robustly and reproducibly. The zebrafish posterior lateral line primordium (PLLp), a group of approximately 120 cells which migrates from the otic vesicle to the tip of the tail, spearheading the development of the lateral line sensory system, is an excellent model to study such collective migration in an in vivo context. This system migrates in a channel formed by the underlying horizontal myoseptum and somites, and the overlying skin. While cells in the leading part of the PLLp are flat and have a more mesenchymal morphology, cells in the trailing part progressively reorganize to form epithelial rosettes, called protoneuromasts. These epithelial cells extend basal cryptic lamellipodia in the direction of migration in response to both chemokine and FGF signals. In this study, we show that, in addition to these cryptic lamellipodia, the core epithelial cells are in fact surrounded by a population of motile cells which extend actin-rich migratory processes apposed to the overlying skin. These thin cells wrap around the protoneuromasts, forming a continuous sheath of cells around the apical and lateral surface of the PLLp. The processes extended by these cells are highly polarized in the direction of migration and this directionality, like that of the basal lamellipodia, is dependent on FGF signaling. Consistent with interactions of sheath cells with the overlying skin contributing to migration, removal of the skin stalls migration. However, this is accompanied by some surprising changes. There is a profound change in the morphology of the sheath cells, with directional superficial lamellipodia being replaced with the appearance of undirected blebs or ruffles. Furthermore, removal of the skin not only affects underlying lamellipodia, it simultaneously alters the morphology and behavior of the deeper basal cryptic lamellipodia, even though these cells do not directly contact the skin. Directional actin-rich protrusions on both the apical and basal surface and migration are completely and simultaneously restored upon regrowth of the skin over the PLLp. We suggest that this system utilizes a circumferential sheath of motile cells to allow the internal epithelial cells to migrate collectively in the confined space of the horizontal myopseptum and that elastic confinement provided by the overlying skin is essential for effective collective migratory behavior of primordium cells.

cell biology↗