Biology subjects

Jenett, A.

Publications and source records attributed to Jenett, A..

6 recordsLinked to original sources

bioRxiv2026

I. Phantom: a multiplex CRISPR-Cas9 gRNA toolkit for efficient generation of fully unpigmented F0 zebrafish

Zebrafish are an increasingly popular model organism, valued for their natural transparency during embryonic stages. However, imaging at later developmental stages is affected by several types of pigments distributed over the body surface. These pigments partially or completely absorb or reflect light, and some also exhibit fluorescence, thereby interfering with imaging. Chemical approaches, such as phenylthiourea (PTU), are available to address this problem. However, PTU only inhibits melanin production and can affect development, making its use controversial. Many mutant zebrafish lines lacking single pigments have already been described, and combinations of melanin and iridophore deficient lines such as the casper and crystal fish greatly improved in vivo imaging at late stages. However, breeding multiple recessive mutations with a desired reporter transgene is laborious, and xanthophores remain in these lines. Here, we address these limitations by developing and optimising a multiplex CRISPR-Cas9 gRNA set that simultaneously targets the three major pigment types, while minimising mortality. This approach generates a new phenotype, termed phantom, characterised by the complete absence of visible pigmentation directly in F0 zebrafish larvae, while retaining the ability to survive to adulthood and reproduce.

molecular biology↗

bioRxiv2026

Pdgfrβ signaling orchestrates meningeal repair via the mobilization of arachnoid cells.

Zebrafish possess remarkable regeneration abilities, including the capacity to repair their central nervous system (CNS). Leveraging the optical accessibility of the zebrafish brain, we investigated the mechanisms underlying meningeal repair following laser-induced brain injuries to the optic tectum. In previous work, using live imaging of laser-induced surface injuries to the optic tectum in juvenile zebrafish, we identified a population of flat PDGFR{beta}+ cells that rapidly migrate to the wound site and contribute to meningeal repair. Here, using pharmacological inhibition or genetic perturbation of PDGFR{beta}, we show that recruitment of these PDGFR{beta}+ meningeal cells is strongly dependent on PDGFR{beta} signaling, unlike recruitment of PDGFR{beta}+ pericytes deeper in the wound. Furthermore, PDGFR{beta} inhibition diminishes neurite regrowth and macrophage recruitment. Using photoconversion assays, we traced the origin of PDGFR{beta}+ meningeal cells that migrated to the wound in response to injury, in the midbrain-forebrain and midbrain-hindbrain sulci. Our findings highlight PDGFR{beta}s pivotal role in orchestrating meningeal repair and reveal novel cellular dynamics during CNS regeneration. These results provide insights into potential therapeutic strategies for enhancing brain repair and mitigating fibrosis in mammals, where meningeal scarring remains a barrier to CNS regeneration. HighlightsPDGFR{beta} signaling orchestrates the rapid accumulation of meningeal cells at CNS injury sites to drive tissue remodeling. PDGFR activity acts as a critical regulator, co-recruiting PDGFR{beta}+ meningeal cells and mfap4+ macrophages to the lesion. Meningeal cells are essential for neural repair, with PDGFR inhibition leading to significantly reduced neurite density. Zebrafish maintain locomotor resilience post-injury, identifying a clear distinction between meningeal-driven axonal regrowth and basic motor circuitry recovery. Establishes a high-resolution zebrafish platform to identify conserved meningeal targets for mammalian CNS regeneration.

cell biology↗

bioRxiv2024

ASTROGLIOSIS AND NEUROINFLAMMATION UNDERLIE SCOLIOSIS UPON CILIA DYSFUNCTION

Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene. Here, we dissected the mechanisms of scoliosis onset in a zebrafish mutant for the rpgrip1l gene encoding a ciliary transition zone protein. rpgrip1l mutant fish developed scoliosis with near-total penetrance but asynchronous onset in juveniles. Taking advantage of this asynchrony, we found that curvature onset was preceded by ventricle dilations and was concomitant to the perturbation of Reissner fiber polymerization and to the loss of multiciliated tufts around the subcommissural organ. Rescue experiments showed that Rpgrip1l was exclusively required in foxj1a-expressing cells to prevent axis curvature. Genetic interactions investigations ruled out Urp1/2 levels as a main driver of scoliosis in rpgrip1 mutants. Transcriptomic and proteomic studies identified neuroinflammation associated with increased Annexin levels as a potential mechanism of scoliosis development in rpgrip1l juveniles. Investigating the cell types associated with annexin2 over-expression, we uncovered astrogliosis, arising in glial cells surrounding the diencephalic and rhombencephalic ventricles just before scoliosis onset and increasing with time in severity. Anti-inflammatory drug treatment reduced scoliosis penetrance and severity and this correlated with reduced astrogliosis and macrophage/microglia enrichment around the diencephalic ventricle. Mutation of the cep290 gene encoding another transition zone protein also associated astrogliosis with scoliosis. Thus, we propose astrogliosis induced by perturbed ventricular homeostasis and associated with immune cell activation as a novel pathogenic mechanism of zebrafish scoliosis caused by cilia dysfunction.

developmental biology↗

bioRxiv2022

Different ways of evolving tool-using brains in teleosts and amniotes

In mammals and birds, tool-using species are characterized by a high degree of encephalization with a relatively large telencephalon containing a higher proportion of total brain neurons compared to other species. Some teleost species in the wrasse family have convergently evolved tool-using abilities. In this study, we compared the brains of tool-using wrasses with various teleost species from a broad phylogenetic range. Using the isotropic fractionator, we show that in the tool-using wrasses, the telencephalon and the ventral part of the forebrain and midbrain are significantly enlarged compared to other teleost species but do not contain a larger proportion of cells. Instead, we found with tract tracing and selective neuronal fiber visualization that this size difference is due to large fiber tracts connecting the dorsal part of the telencephalon (pallium) to the inferior lobe (IL), a ventral mesencephalic structure absent in amniotes. The high degree of connectivity between the IL and the pallium in tool-using wrasses suggests that this unique teleostean structure could contribute to higher-order cognitive functions. Given remarkable differences in their overall brain organization, we conclude that, unlike in amniotes, the evolution of non-telencephalic structures might have been key in the emergence of higher-order cognitive functions in teleosts.

neuroscience↗

bioRxiv2020

ZeBraInspector, a whole organism screening platform enabling volumetric analysis of zebrafish brain white matter

In recent years, the zebrafish has become a well-established laboratory model. We describe here the ZeBraInspector (ZBI) platform for high-content 3D imaging (HCI) of 5 dpf zebrafish eleuthero-embryos (EEs). This platform includes a mounting method based on 3D-printed stamps to create a grid of wells in an agarose cast, facilitating batch acquisitions with a fast-confocal laser scanning microscope. We describe reference labeling in cleared fish with a fluorescent lipophilic dye. Based on this labeling, the ZBI software registers EE 3D images, making it possible to visualize numerous identically oriented EEs on a single screen, and to compare their morphologies and any fluorescent patterns at a glance. High-resolution 2D snapshots can be extracted. ZBI software is therefore useful for diverse high-content analyses (HCAs). Following automated segmentation of the lipophilic dye signal, the ZBI software performs volumetric analyses on whole EEs and their nervous system white matter. Through two examples, we illustrate the power of these analyses for obtaining statistically significant results from a small number of samples: the characterization of a phenotype associated with a neurodevelopmental mutation, and of the defects caused by treatments with a toxic anti-cancer compound.

neuroscience↗

bioRxiv2020

Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts

Ascending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homologous relationship is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a visual relay nucleus in zebrafish (a teleost fish). Similarly to the tectofugal visual thalamic nuclei in amniotes, the lateral part of the preglomerular complex (PG) in teleosts receives tectal information and projects to the pallium. However, our cell lineage study reveals that the majority of PG cells are derived from the midbrain, not from the forebrain. We also demonstrate that the PG projection neurons develop gradually until juvenile stage, unlike the thalamic projection neurons. Our data suggest that teleost PG is not homologous to the amniote thalamus and that thalamocortical-like projections can evolve from a non-forebrain cell population. Thus, sensory pathways in vertebrate brains exhibit a surprising degree of variation.

neuroscience↗