Biology subjects

van Leeuwen, T.

Publications and source records attributed to van Leeuwen, T..

5 recordsLinked to original sources

bioRxiv2024

Polytope: High-resolution epitope barcoding for in vivo spatial fate-mapping

Tracing the fate of individual cells and their progeny remains a challenging task. While imaging-based fate-mapping provides spatial information, it generally lacks complexity due to limited label diversity, resulting in diminished capture of comprehensive lineages and fate maps. Here, we introduce Polytope, an epitope barcoding system capable of generating up to 512 unique color codes. Comprising nine epitope tag cassettes flanked by loxP sites, Polytope allows random excision via Cre recombinase, creating unique color codes detectable through multiplexed imaging. Using an engineered Polytope mouse, we traced the fate of hundreds of clones across tissues in vivo, from embryonic development until adulthood. Together, Polytope enables high-resolution imaging-based fate-mapping through endogenous epitope barcoding, comprehensively capturing the spatial organization of complex clonal dynamics in situ. One-Sentence SummaryPolytope is an imaging-based barcoding system to trace lineages at clonal and spatial resolution in living organisms using a diverse set of color-coded markers.

developmental biology↗

bioRxiv2024

Pupil dilation offers a time-window on prediction error

Task-evoked pupil dilation has been linked to many cognitive variables, perhaps most notably unexpected events. Zenon (2019) proposed a unifying framework stating that pupil dilation related to cognition should be considered from an information-theory perspective. In the current study, we investigated whether the pupils response to decision outcome in the context of associative learning reflects a prediction error signal defined operationally as an interaction between stimulus-pair frequency and accuracy, while also exploring the time course of this prediction error signal. Thereafter, we tested whether these prediction error signals correlated with information gain, defined formally as the KL divergence between posterior and prior belief distributions of the ideal observer. We reasoned that information gain should be proportional to the (precision-weighted) prediction error signals potentially arising from neuromodulatory arousal networks. To do so, we adapted a simple model of trial-by-trial learning of stimulus probabilities based on information theory from previous literature. We analyzed two data sets in which participants performed perceptual decision-making tasks that required associative learning while pupil dilation was recorded. Our findings consistently showed that a significant proportion of variability in the post-feedback pupil response during decision-making can be explained by a formal quantification of information gain shortly after feedback presentation in both task contexts. In the later time window, the relationship between information-theoretic variables and the post-feedback pupil response differed per task. For the first time, we present evidence that whether the post-feedback pupil dilates or constricts along with information gain was context dependent. This study offers empirical evidence showcasing how the pupils response can offer valuable insights into the process of model updating during learning, highlighting the promising utility of this readily accessible physiological indicator for investigating internal belief states.

neuroscience↗

bioRxiv2023

Psycho-spatially distinct stressors prompt distinct behavioral strategies through a cell type-specific brain circuit

Adaptive behavioral responses to stressors are critical for survival. However, which brain areas orchestrate switching the appropriate stress responses to distinct contexts is an open question. This study aimed to identify the cell type-specific brain circuitry governing the selection of distinct behavioral strategies in response to stressors. Through novel mouse behavior paradigms, we observed distinct stressor-evoked behaviors in two psycho-spatially distinct contexts, characterized by stressors inside or outside the safe zone. The identification of brain regions activated in both conditions revealed the involvement of the dorsomedial hypothalamus (DMH). Further investigation using optogenetics, chemogenetics, and photometry uncovered that glutamatergic projections from the DMH to periaqueductal gray (PAG) mediated responses to inside-stressors, while GABAergic projections, particularly from tachykinin1-expressing neurons, played a crucial role in coping with outside-stressors. These findings elucidate the role of cell type-specific circuitry from the DMH to the PAG in shaping behavioral strategies in response to stressors. These findings have the potential to advance our understanding of fundamental neurobiological processes and inform the development of novel approaches for managing context-dependent and anxiety-associated pathological conditions such as agoraphobia and claustrophobia.

neuroscience↗

bioRxiv2022

Anatomy of the complete mouse eye vasculature indevelopment and pathology explored by light-sheet fluorescence microscopy

Eye development and function rely on precise establishment, regression and maintenance of its many sub-vasculatures. These crucial vascular properties have been extensively investigated in eye development and disease utilizing genetic and experimental mouse models. However, due to technical limitations, individual studies have often restricted their focus to one specific sub-vasculature. Here, we apply a workflow that allows for visualisation of complete vasculatures of mouse eyes of various developmental stages. Through tissue depigmentation, immunostaining, clearing and light-sheet fluorescence microscopy (LSFM) entire vasculatures of the retina, vitreous (hyaloids) and uvea were simultaneously imaged at high resolution. In silico dissection provided detailed information on their 3D architecture and interconnections. By this method we describe remodelling of the postnatal iris vasculature following its disconnection to the feeding hyaloid vasculature. In addition, we demonstrate examples of conventional and LSFM-mediated analysis of choroidal neovascularisation after laser-induced wounding, showing added value of the presented workflow in analysis of modelled eye disease. These advancements in visualisation and analysis of the respective eye vasculatures in development and complex eye disease open for novel observations of their functional interplay at a whole-organ level.

developmental biology↗

bioRxiv2020

A scientometric overview of CORD-19

As the COVID-19 pandemic unfolds, researchers from all disciplines are coming together and contributing their expertise. CORD-19, a dataset of COVID-19 and coronavirus publications, has been made available along-side calls to help mine the information it contains and to create tools to search it more effectively. We analyse the delineation of the publications included in CORD-19 from a scientometric perspective. Based on a comparison to the Web of Science database, we find that CORD-19 provides an almost complete coverage of research on COVID-19 and coronaviruses. CORD-19 contains not only research that deals directly with COVID-19 and coronaviruses, but also research on viruses in general. Publications from CORD-19 focus mostly on a few well-defined research areas, in particular: coronaviruses (primarily SARS-CoV, MERS-CoV and SARS-CoV-2); public health and viral epidemics; molecular biology of viruses; influenza and other families of viruses; immunology and antivirals; clinical medicine. CORD-19 publications that appeared in 2020, especially editorials and letters, are disproportionately popular on social media. While we fully endorse the CORD-19 initiative, it is important to be aware that CORD-19 extends beyond research on COVID-19 and coronaviruses.

scientific communication and education↗