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Pezeron, G.

Publications and source records attributed to Pezeron, G..

4 recordsLinked to original sources

Hormonal gene expression changes in the zebrafish caudal neurosecretory system under acute environmental challenges

The caudal neurosecretory system (CNSS) is a neuroendocrine complex, found only in fishes, suggested to be involved in osmoregulation and thermo-adaptation. Although being discovered 70 years ago, the CNSS has been understudied and its physiological significance remains poorly understood. The zebrafish (Danio rerio) is a well-established model organism for functional studies, yet, so far, the role of the CNSS has not really been investigated in this species. In the present study, we attempted to identify environmental factors whose variations induce changes in CNSS activity. Juvenile zebrafish were submitted to acute (2 h, 8 h, and 24 h) pH, salinity, and temperature challenges, and CNSS activity was quantified by measuring the expression levels of peptide hormone-encoding genes using quantitative PCR. Our findings revealed that temperature challenge affected the expression of the largest number of gene, followed by salinity and pH challenges. This suggested that, in the zebrafish, the CNSS is involved in thermo-adaptation and osmoregulation, which is consistent with what has been reported in other species, and showed that the zebrafish is a relevant model to study the function of the CNSS.

physiology↗

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↗

Urp1 and Urp2 act redundantly to maintain spine shape in zebrafish larvae.

Urp1 and Urp2 are two neuropeptides, members of the Urotensin 2 family, that have been recently involved in the control of body axis morphogenesis in zebrafish. They are produced by a population of sensory spinal neurons, called cerebrospinal fluid contacting neurons (CSF-cNs), under the control of signals relying on the Reissner fiber, an extracellular thread bathing in the CSF. Here, we have investigated further the function of Urp1 and Urp2 (Urp1/2) in body axis formation and maintenance. We showed that urp1;urp2 double mutants develop strong body axis defects during larval growth, revealing the redundancy between the two neuropeptides. These defects were similar to those previously reported in uts2r3 mutants. We observed that this phenotype is not associated with bone formation defects nor with increased inflammation status but, by using specific inhibitors, we found that the action of Urp1/2 depends on myosin II contraction. Finally, we provide evidence that while the Urp1/2 signaling is functioning during larval growth but is dispensable for embryonic development. Taken together, our results show that Urp1/2 signaling is required in larvae to promote correct vertebral body axis, most likely by regulating muscle tone.

developmental biology↗

Adrenergic activation modulates the signal from the Reissner fiber to cerebrospinal fluid-contacting neurons during development

The cerebrospinal fluid (CSF) contains an extracellular thread that is conserved in vertebrates and referred to as the Reissner fiber. Genetic ablation in the zebrafish revealed that the Reissner fiber controls body axis morphogenesis in the embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not fully understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required for the expression of urp2, a neuropeptide expressed in CSF-cNs. Using in vivo calcium imaging, we show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation directly in the CSF can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results suggest that the Reissner fiber acts on CSF-cNs to establish body axis morphogensis by controlling the availability of a chemical signal in the CSF.

developmental biology↗