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Colin, I.

Publications and source records attributed to Colin, I..

3 recordsLinked to original sources

The two groups of zebrafish type I interferons target different tissues, paralleling the mammalian type I: type III IFN functional division

Interferons (IFNs) are ancient cytokines that arose in jawed vertebrates [~]400-500 million years ago. IFN systems are present with conserved antiviral functions across vertebrate lineages, including zebrafish (Danio rerio). In mammals, antiviral IFNs are divided between type I interferons (IFN-I), which drive systemic responses, and type III interferons (IFN-III), which protect barrier mucosal epithelia, owing to the specific distribution of their respective receptors. Although zebrafish lack IFN-III, they have IFN-Is which subdivide into 2 groups with distinct receptors, providing a unique opportunity to study how antiviral immunity has evolved in the absence of IFN-III. Whilst previous work has suggested complementary, non-redundant roles for IFNs from these groups, the tissue specificity has not yet been resolved. As larvae, zebrafish only express one group 1 (IFN{varphi}1) and one group 2 IFN (IFN{varphi}3). Using viral infection assays and reporter transgenics, we found that IFNs from group 1 (IFN{varphi}1) and group 2 (IFN{varphi}3) are produced by distinct subsets of cells, with no detectable co-expression. To assess tissue and cell-type-specific responses to these two IFNs, we used ISG reporter fish imaging and whole-larva single cell RNA sequencing after injection of recombinant IFN{varphi}1 and IFN{varphi}3. Despite a similar core ISG response, distinct downstream ISG programs across multiple tissues and organ systems were found. In particular, barrier epithelial cells, such as enterocytes, responded more strongly to IFN{varphi}1, while myeloid cells responded more strongly to IFN{varphi}3. Our results indicate that zebrafish IFN-I families have functionally diversified their antiviral immune responses by tissue context, driven by cellular partitioning of both IFN-I production and response. These results mirror the division of labour between mammalian IFN-I and IFN-III, emphasising the evolutionary importance of tissue division of immune responses, as well as deepening our understanding of the zebrafish as a model for host-pathogen interactions.

immunology↗

Plasticity of the dopaminergic phenotype and of locomotion in larval zebrafish induced by changes in brain excitability during the embryonic period.

During the embryonic period, neuronal communication starts before the establishment of the synapses with alternative forms of neuronal excitability, called here Embryonic Neuronal Excitability (ENE). ENE has been shown to modulate the unfolding of development transcriptional programs but the global consequences for the developing organisms are not all understood. Here we monitored calcium transients in zebrafish embryos as a proxy for ENE to assess the efficacy of transient pharmacological treatments to either increase or decrease ENE. Increasing or decreasing ENE for 24 hours at 2 days post fertilization (dpf), at the end of the embryonic period, promoted respectively an increase or a decrease in the numbers of dopamine (DA) neurons in the telencephalon and in the olfactory bulb of zebrafish larvae at 6 dpf. This plasticity of dopaminergic specification occurs within a stable population of vMAT2-positive cells, hence identifying an unanticipated biological marker for this reserve pool of of DA neurons that can be recruited by increasing ENE. Modulating ENE also affected larval locomotion several days after the end of the treatments. In particular, the increase of ENE from 2 to 3 dpf promoted hyperlocomotion of larvae at 6 dpf, reminiscent of endophenotypes reported for Attention Deficit with Hyperactivity Disorders and schizophrenia in zebrafish. These results provide a convenient framework to identify environmental factors that could disturb ENE as well as to study the molecular mechanisms linking ENE to neurotransmitter specification, with relevance to the pathogenesis of neurodevelopmental disorders. Significance Statement- Spontaneous calcium transients, used as a proxy for Embryonic Neuronal Excitability (ENE), are detected in the forebrain of embryonic zebrafish. - Short-term pharmacological treatments by bath application could increase or decrease ENE. - The post-mitotic differentiation of the dopaminergic phenotype is modulated by ENE in the zebrafish forebrain. - The plasticity of the dopaminergic specification occurs within a reserve pool of vMAT2-positive cells. - Transient increase of ENE at the end of the embryonic period induces hyperlocomotion, a phenotype associated with ADHD and schizophrenia in this model. - Our results open clinically relevant perspectives to study the pathogenesis of neurodevelopmental disorders in zebrafish.

neuroscience↗

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↗