Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU) or in situ hybridizations for cell type markers (Vimentin, Sox2). We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA-) cells and not radial glial (Vimentin+) or progenitors (Sox2+) cells.
ISSN: 1932-6203

hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877023/file/The_Neurogenic_Factor-accepted.pdf
DOI : 10.1371/journal.pone.0066487

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The last step of oestrogen biosynthesis is catalyzed by the enzyme aromatase, the product of the cyp19a1 gene. In vertebrates, cyp19a1 is expressed in the brain resulting in a local oestrogen production that seems important not only for the control of reproduction-related circuits and sexual behaviour, but also for the regulation of neural development, synaptic plasticity and cell survival. In adult amphibians, the precise sites of expression of cyp19a1 in the brain have not been investigated which prevents proper understanding of its potential physiological functions. The present study aimed at examining the precise neuroanatomical distribution of cyp19a1 transcripts in adult brains of both male and female Xenopus. We found that cyp19a1 expression is highly regionalized in the brains of both sexes. The highest expression was found in the anterior part of the preoptic area and in the caudal hypothalamus, but significant levels of cyp19a1 transcripts were also found in the supraoptic paraventricular and suprachiasmatic areas, and in brain regions corresponding to the septum, bed nucleus of the stria terminalis and amygdala. Importantly, no obvious difference between male and female Xenopus was detected at the level of cyp19a1 transcripts. Additionally, in the brain of adult Xenopus, cyp19a1 transcripts were detected in neurons, and not in glial cells. These data and those available in other vertebrates on cyp19a1/aromatase expression suggest that, with the intriguing exception of teleost fishes, cyp19a1 was under strong evolutionary conservation with respect to its sites of expression and the nature of the cells in which it is expressed
ISSN: 0016-6480

hal-01187140
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187140
DOI : 10.1016/j.ygcen.2015.08.008
PUBMED : 26255686

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Second harmonic generation (SHG) microscopy is a powerful tool for studying submicron architecture of muscles tissues. Using this technique, we show that the canonical single frequency sarcomeric SHG intensity pattern (SHG-IP) of premetamorphic xenopus tadpole tail muscles is converted to double frequency (2f) sarcomeric SHG-IP in metamorphic climax stages due to massive physiological muscle proteolysis. This conversion was found to rise from 7% in premetamorphic muscles to about 97% in fragmented muscular apoptotic bodies. Moreover a 66% conversion was also found in non-fragmented metamorphic tail muscles. Also, a strong correlation between predominant 2f sarcomeric SHG-IPs and myofibrillar misalignment is established with electron microscopy. Experimental and theoretical results demonstrate the higher sensitivity and the supra resolution power of SHG microscopy over TPEF to reveal 3D myofibrillar misalignment. From this study, we suggest that 2f sarcomeric SHG-IP could be used as signature of triad defect and disruption of excitation–contraction coupling. As the mechanism of muscle proteolysis is similar to that found in mdx mouse muscles, we further suggest that xenopus tadpole tail resorption at climax stages could be used as an alternative or complementary model of Duchene muscular dystrophy.
ISSN: 1047-8477

hal-01134174
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174/file/Recher%20et%20al_JSB-2015_hal.pdf
DOI : 10.1016/j.jsb.2015.03.003

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Cytochrome P450 aromatase (P450arom; aromatase) is a microsomal enzyme involved in the production of endogeneous sex steroids by converting testosterone into oestradiol. Aromatase is the product of the cyp19a1 gene and plays a crucial role in the sexual differentiation of the brain and in the regulation of reproductive functions. In the brain of mammals and birds, expression of cyp19a1 has been demonstrated in neuronal populations of the telencephalon and diencephalon. By contrast, a wealth of evidence established that, in teleost fishes, aromatase expression in the brain is restricted to radial glial cells. The present study investigated the precise neuroanatomical distribution of cyp19a1 mRNA during brain development in Xenopus laevis (late embryonic to juvenile stages). For this purpose, we used in situ hybridisation alone or combined with the detection of a proliferative (proliferating cell nuclear antigen), glial (brain lipid binding protein, Vimentin) or neuronal (acetylated tubulin; HuC/D; NeuroβTubulin) markers. We provide evidence that cyp19a1 expression in the brain is initiated from the very early larval stage and remains strongly detected until the juvenile and adult stages. At all stages analysed, we found the highest expression of cyp19a1 in the preoptic area and the hypothalamus compared to the rest of the brain. In these two brain regions, cyp19a1-positive cells were never detected in the ventricular layers. Indeed, no co-labelling could be observed with radial glial (brain lipid binding protein, Vimentin) or dividing progenitors (proliferating cell nuclear antigen) markers. By contrast, cyp19a1-positive cells perfectly matched with the distribution of post-mitotic neurones as shown by the use of specific markers (HuC/D, acetylated tubulin and NeuroβTubulin). These data suggest that, similar to that found in other tetrapods, aromatase in the brain of amphibians is found in post-mitotic neurones and not in radial glia as reported in teleosts.
ISSN: 0953-8194

hal-00994513
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00994513
DOI : 10.1111/jne.12142
PUBMED : 24612124

Éditeur(s) : HAL CCSD Royal Society
Résumé : International audience
Maternal Embryonic Leucine zipper Kinase (MELK) was recently shown to be involved in cell division of Xenopus embryo epithelial cells. The cytokinetic furrow of these cells ingresses asymmetrically and is developmentally regulated. Two subpopulations of xMELK, the mMELK (for "mitotic" xMELK) and iMELK ("interphase" xMELK), which differ in their spatial and temporal regulation, are detected in Xenopus embryo. How cells regulate these two xMELK populations is unknown. In this study we show that, in epithelial cells, xMELK is present at a higher concentration at the apical junctional complex, in contrast to mesenchyme-like cells, which have uniform distribution of cortical MELK. Interestingly, mMELK and iMELK also differ by their requirements towards cell-cell contacts to establish their proper cortical localization both in epithelial and mesenchyme-like cells. Receptor for Activated protein Kinase C (RACK1), which we identified as an xMELK partner, co-localizes with xMELK at the tight junction. Moreover, a truncated RACK1 construct interferes with iMELK localization at cell-cell contacts. Collectively, our results suggest that iMELK and RACK1 are present in the same complex and that RACK1 is involved in the specific recruitment of iMELK at the apical junctional complex in epithelial cells of Xenopus embryos.
ISSN: 2046-6390

hal-00874053
https://hal.archives-ouvertes.fr/hal-00874053
https://hal.archives-ouvertes.fr/hal-00874053/document
https://hal.archives-ouvertes.fr/hal-00874053/file/Cell-cycle_dependent-accepted.pdf
DOI : 10.1242/bio.20136080

Éditeur(s) : HAL CCSD
Résumé : International audience
Estrogens affect brain development of vertebrates, not only by impacting activity and morphology of existing circuits, but also by modulating embryonic and adult neurogenesis. The issue is complex as estrogens can not only originate from peripheral tissues, but also be locally produced within the brain itself due to local aromatization of androgens. In this respect, teleost fishes are quite unique because aromatase is expressed exclusively in radial glial cells, which represent pluripotent cells in the brain of all vertebrates. Expression of aromatase in the brain of fish is also strongly stimulated by estrogens and some androgens. This creates a very intriguing positive auto-regulatory loop leading to dramatic aromatase expression in sexually mature fish with elevated levels of circulating steroids. Looking at the effects of estrogens or anti-estrogens in the brain of adult zebrafish showed that estrogens inhibit rather than stimulate cell proliferation and newborn cell migration. The functional meaning of these observations is still unclear, but these data suggest that the brain of fish is experiencing constant remodeling under the influence of circulating steroids and brain-derived neurosteroids, possibly permitting a diversification of sexual strategies, notably hermaphroditism. Recent data in frogs indicate that aromatase expression is limited to neurons and do not concern radial glial cells. Thus, until now, there is no other example of vertebrates in which radial progenitors express aromatase. This raises the question of when and why these new features were gained and what are their adaptive benefits. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Droits : info:eu-repo/semantics/OpenAccess
hal-01102449
https://hal.archives-ouvertes.fr/hal-01102449
https://hal.archives-ouvertes.fr/hal-01102449/document
https://hal.archives-ouvertes.fr/hal-01102449/file/Coumailleau%20et%20al%20final%20manuscript.pdf
DOI : 10.1016/j.bbagrm.2014.07.002

Éditeur(s) : HAL CCSD
Résumé : International audience
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. © 2016 Wiley Periodicals, Inc.
Journal of Comparative Neurology

hal-01439354
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01439354
DOI : 10.1002/cne.24077
PUBMED : 27414756