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Mazan, S.

Publications and source records attributed to Mazan, S..

7 recordsLinked to original sources

A single-nucleus RNA sequencing atlas of the postnatal retina of the shark Scyliorhinus canicula

The retina, whose basic cellular structure is highly conserved across vertebrates, constitutes an accessible system for studying the central nervous system. In recent years, single-cell RNA-sequencing studies have uncovered cellular diversity in the retina of a variety of species, providing new insights on retinal evolution and development. However, similar data in cartilaginous fishes, the sister group to all other extant jawed vertebrates, are still lacking. Here, we present a single-nucleus RNA-sequencing atlas of the postnatal retina of the catshark Scyliorhinus canicula, consisting of the expression profiles for 17,438 individual cells from three female, juvenile catshark specimens. Unsupervised clustering revealed 22 distinct cell types comprising all major retinal cell classes, as well as retinal progenitor cells (whose presence reflects the persistence of proliferative activity in postnatal stages in sharks) and oligodendrocytes. Thus, our dataset serves as a foundation for further studies on the development and function of the catshark retina. Moreover, integration of our atlas with data from other species will allow for a better understanding of vertebrate retinal evolution.

neuroscience↗

3D RNA profile of habenulae in the catshark Scyliorhinus canicula: a reference in jawed vertebrates

We report the generation of a spatially resolved RNA profile of the habenulae in a chondrichthyan, the catshark Scyliorhinus canicula. The digital profiles obtained for candidate markers of the broad territories previously characterized in this species reflect their broad characteristics, including left- or right asymmetric distributions. We use spatial autocorrelation and autocorrelation as measures to analyze these data and identify novel territory markers. These analyses lead to a refined molecular characterization of catshark habenulae and lead to extended lists of markers for the major territories previously identified. They confirm the marked asymmetry of the catshark habenulae, both in its lateral and medial components. In addition, they highlight a bilateral lateral to medial organization in radial bands, which may reflect a temporal regulation of neurogenesis. These data lead to a novel reference to explore the lmode of evolution of habenulae and of their asymmetries across gnathostomes.

developmental biology↗

Evolutionary Origin of Vertebrate OCT4/POU5 Functions in Supporting Pluripotency

The support of pluripotent cells over time is an essential feature of development. In eutherian embryos, pluripotency is maintained from naive states in peri-implantation to primed pluripotency at gastrulation. To understand how these states emerged, we reconstruct the evolutionary trajectory of the Pou5 gene family, which contains the central pluripotency factor OCT4. By coupling evolutionary sequence analysis with functional studies in mouse Embryonic Stem Cells (ESCs), we found that the ability of POU5 proteins to support pluripotency originated in the gnathostome lineage, prior to the generation of two paralogues, Pou5f1 and Pou5f3 via gene duplication. In osteichthyans, retaining both genes, the paralogues differ in their support of naive and primed pluripotency. This specialization of these duplicates enables the diversification of function in self-renewal and differentiation. By integrating sequence evolution, ESC phenotypes, developmental contexts and structural modelling, we pinpoint OCT4 regions sufficient for naive pluripotency and describe their adaptation over evolutionary time.

developmental biology↗

Evolution of lbx spinal cord expression and function

Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. Amniotes have two Lbx genes, but only Lbx1 is expressed in spinal cord. In contrast, teleosts have three lbx genes and we show here that zebrafish lbx1a, lbx1b and lbx2 are expressed by distinct spinal cell types, and that lbx1a is expressed in dI4, dI5 and dI6 interneurons, as in amniotes. Our data examining lbx expression in Scyliorhinus canicula and Xenopus tropicalis suggest that the spinal interneuron expression of zebrafish lbx1a is ancestral, whereas lbx1b has acquired a new expression pattern in spinal cord progenitor cells. lbx2 spinal expression was probably acquired in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. We also show that the spinal function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction in the number of inhibitory spinal interneurons and an increase in the number of excitatory spinal interneurons, similar to mouse Lbx1 mutants. Interestingly, the number of inhibitory spinal interneurons is also reduced in lbx1b mutants, although in this case the number of excitatory interneurons is not increased. lbx1a;lbx1b double mutants have a similar spinal interneuron phenotype to lbx1a single mutants. Taken together these data suggest that lbx1b and lbx1a may be required in succession for correct specification of dI4 and dI6 spinal interneurons, although only lbx1a is required for suppression of excitatory fates in these cells. Research Highlightslbx1 spinal expression and function is conserved in vertebrates. In contrast, zebrafish lbx1b and lbx2 have novel spinal expression patterns that probably evolved in the ray-finned vertebrate lineage (lbx2) or teleosts (lbx1b).

developmental biology↗

Loss of active neurogenesis in the adult shark retina

Neurogenesis is the process by which progenitor cells generate new neurons. As development progresses neurogenesis becomes restricted to concrete neurogenic niches, where it persists during postnatal life. The retina of teleost fishes is thought to proliferate and produce new cells throughout life. Whether this capacity may be an ancestral characteristic of jawed vertebrates, shared with chondrichthyans, which diverged from osteichthyans prior to the gnathostome radiation is completely unknown. Previous work from our group revealed that the juvenile retina of the catshark Scyliorhinus canicula shows active proliferation and neurogenesis. Here, we compared the morphology and proliferative status of the retina between catshark juveniles and adults. Histological analyses revealed an important reduction in the size of the peripheral retina (where progenitor cells are mainly located), an increase in the thickness of the plexiform layers and a decrease in the thickness of the inner nuclear layer in adults. Contrary to what has been reported in teleost fish, we did not observe active mitotic activity in the catshark retina after sexual maturation, suggesting that there is no significant proliferation and neurogenesis in adult specimens. Based on these results, we carried out RNA-Sequencing (RNA-Seq) analyses comparing the retinal transcriptome of juveniles and adults, which revealed a statistically significant decrease in the expression of many genes involved in cell proliferation and neurogenesis in adult catsharks. Our RNA-Seq data provides an excellent resource to identify new signaling pathways controlling neurogenesis in the vertebrate retina.

developmental biology↗

Differential expression of five prosomatostatin genes in the central nervous system of the catshark Scyliorhinus canicula

Five prosomatostatin genes (PSST1, PSST2, PSST3, PSST5 and PSST6) have been recently identified in elasmobranchs (Tostivint, Gaillard, Mazan, & Pezeron, 2019). In order to gain insight into the contribution of each somatostatin to specific nervous systems circuits and behaviors in this important jawed vertebrate group, we studied the distribution of neurons expressing PSST mRNAs in the catshark Scyliorhinus canicula using in situ hybridization with specific probes for the five PSSTs transcripts. Additionally, we combined in situ hybridization with tyrosine hydroxylase (TH) immunochemistry for better localization of some PSSTs-positive populations. The five PSST genes showed expression in the brain, although with important differences in distribution. PSST1 and PSST6 were widely expressed in different brain regions. Instead, PSST2 and PSST3 were expressed only in the ventral hypothalamus and in some hindbrain lateral reticular neurons, whereas PSST5 was only expressed in the region of the entopeduncular nucleus. PSST1 and PSST6 were expressed by numerous pallial neurons, although in different populations judging from the colocalization of tyrosine hydroxylase (TH) immunoreactivity and PSST6 expression in pallial neurons and the absence of colocalization between TH and PSST1 expression. Differential expression of PSST1 and PSST6 was also observed in the subpallium, hypothalamus, diencephalon, optic tectum, midbrain tegmentum and rhombencephalon. Expression of PSST1 was observed in numerous cerebrospinal fluid-contacting (CSF-c) neurons of the paraventricular organ of the hypothalamus and the central canal of the spinal cord. These wide differences in expression of PSST genes together with the numerous brain nuclei expressing PSSTs, indicate that catshark somatostatinergic neurons are implicated differentially in a number of neural circuits.

neuroscience↗

Characterization of neurogenic niches in the telencephalon of juvenile and adult sharks

Neurogenesis is a multistep process by which progenitor cells become terminally differentiated neurons. Adult neurogenesis has gathered increasing interest with the aim of developing new cell-based treatments for neurodegenerative diseases in humans. Active sites of adult neurogenesis exist from fish to mammals, although in the adult mammalian brain the number and extension of neurogenic areas is considerably reduced in comparison to non-mammalian vertebrates, and they become mostly reduced to the telencephalon. Much of our understanding in this field is based in studies on mammals and zebrafish, a modern bony fish. The use of the cartilaginous fish Scyliorhinus canicula (representative of basal gnathostomes) as a model expands the comparative framework to a species that shows highly neurogenic activity in the adult brain. In this work, we studied the proliferation pattern in the telencephalon of juvenile and adult specimens of S. canicula by using antibodies against the proliferation marker PCNA. We have characterized proliferating niches by using stem cell markers (Sox2), glial markers (GFAP, BLBP and GS), intermediate progenitor cell markers (Dlx2 and Tbr2) and markers for migrating neuroblasts (DCX). Based in the expression pattern of these markers, we demonstrate the existence of different cell subtypes within the PCNA immunoreactive zones including non-glial stem cells, glial progenitors, intermediate progenitor-like cells and migratory neuroblasts, which were widely distributed in the ventricular zone of the pallium, suggesting that the main progenitor types that constitute the neurogenic niche in mammals are already present in cartilaginous fishes.

neuroscience↗