Biology subjects

Hasel de Carvalho, E.

Publications and source records attributed to Hasel de Carvalho, E..

4 recordsLinked to original sources

bioRxiv2025

Immune surveillance and pruning of neuronal stem cells in the medaka retina

Stem cell populations in tissues require precise regulation of their number and quality to maintain proper organ growth. Amongst various regulatory mechanisms, immune cells are emerging to directly regulate stem cell populations. The medaka retinal stem cell (RSC) niche, a model for lifelong neurogenic growth, provides a system to study immune-stem cell interactions. We investigate how microglia, resident macrophages of the central nervous system, regulate the RSC niche. We identify that bona fide RSCs express the chemokine Ccl25b while its cognate receptor, Ccr9a, is expressed in microglia. These microglia form a surveillance ring adjacent to the RSC niche and actively phagocytose RSCs. Interference with microglia by deletion of spi1b reveals that microglia absence leads to increased numbers of ccl25b-positive RSCs and results in morphological defects of the retina. Targeted mutation of ccl25b specifically affects microglia mobility under injury conditions, however, we did not observe any morphological defects indicating that Ccl25b-Ccr9a signaling is not essential for stem cell maintenance. Overall, our data show that under homeostatic conditions the individual RSCs, essential for proper eye development, are actively phagocytosed by immune surveillance.

developmental biology↗

bioRxiv2022

The Opto-inflammasome in zebrafish: a tool to study cell and tissue responses to speck formation and cell death

The inflammasome is a conserved system for the intracellular detection of danger or pathogen signals. By forming a large intracellular multiprotein signaling platform, it activates downstream effectors that initiate a rapid necrotic programmed cell death (PCD) termed pyroptosis and activation and secretion of pro-inflammatory cytokines to warn and activate surrounding cells. However, inflammasome activation is difficult to control on a single-cell level using canonical triggers. We constructed Opto-Asc, a light-responsive form of the inflammasome adaptor protein ASC (Apoptosis-Associated Speck-Like Protein Containing a CARD) which allows tight control of inflammasome formation in vivo. We introduced a cassette of this construct under the control of a heat shock element into zebrafish in which we can now induce Asc inflammasome (speck) formation in single cells of the skin. We find that cell death resulting from Asc speck formation is morphological distinct from apoptosis in periderm but not in basal cells. Asc induced PCD in can lead to apical or basal extrusion from the periderm. The apical extrusion in periderm cells depends on Caspb but and triggers a strong Ca2+ signaling response in nearby cells.

immunology↗

bioRxiv2022

Revisiting the origin of interleukin 1 (IL-1) based on biological activities of IL-1 in anamniotes and their sub-functionalization in amniotes

The cytokine Interleukin 1 (IL-1) is an evolutionary innovation of vertebrates. Fish and amphibia have one IL1 gene, while mammals have two copies of IL1, IL1A and IL1B, with distinct expression patterns and differences in their proteolytic activation. Our current understanding of the evolutionary history of IL-1 is mainly based on phylogenetic analyses, but this approach provides no information on potentially different functions of IL-1 homologs, and it remains unclear which biological activities identified for IL-1 and IL-1{beta} in mammals are present in lower vertebrates. Here, we use in vitro and in vivo experimental models to examine the expression patterns and cleavage of IL-1 proteins from various species. We found that IL-1 in the teleost medaka shares the transcriptional patterns of mammalian IL-1, and its processing also resembles that of mammalian IL-1, which is sensitive to cysteine protease inhibitors specific for the calpain and cathepsin families. By contrast, IL-1 proteins in reptiles also include biological properties of IL-1{beta}. Therefore, we propose that duplication of the ancestral IL1 gene led to segregation of expression patterns and protein processing that characterizes the two extant forms of IL-1 in mammals.

immunology↗

bioRxiv2021

Optogenetic activators of apoptosis, necroptosis and pyroptosis for probing cell death dynamics and bystander cell responses

Targeted and specific induction of cell death in individual or groups of cells holds the potential for new insights into the response of tissues or organisms to different forms of death. Here we report the development of optogenetically-controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD) - apoptosis, pyroptosis and necroptosis - using Arabidopsis thaliana photosensitive protein Cryptochrome2. OptoCDEs enable rapid and highly specific induction of PCD in human, mouse and zebrafish cells and are suitable for a wide range of applications, such as sub-lethal cell death induction or precise elimination of single cells or cell populations in vitro and in vivo. As the proof-of-concept, we utilize optoCDEs to assess the differences in the neighboring cell response to apoptotic or necrotic PCD, revealing a new role for shingosine-1-phosphate signaling in regulating the efferocytosis of apoptotic cell by epithelia.

cell biology↗