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PubMed | Institute for Neurosciences of Montpellier, University Paris - Sud, Montpellier University, University of Concepción and University Paris Diderot
Type: | Journal: Frontiers in genetics | Year: 2015

Understanding the evolutionary emergence and subsequent diversification of the vertebrate skeleton requires a comprehensive view of the diverse skeletal cell types found in distinct developmental contexts, tissues, and species. To date, our knowledge of the molecular nature of the shark calcified extracellular matrix, and its relationships with osteichthyan skeletal tissues, remain scarce. Here, based on specific combinations of expression patterns of the Col1a1, Col1a2, and Col2a1 fibrillar collagen genes, we compare the molecular footprint of endoskeletal elements from the chondrichthyan Scyliorhinus canicula and the tetrapod Xenopus tropicalis. We find that, depending on the anatomical location, Scyliorhinus skeletal calcification is associated to cell types expressing different subsets of fibrillar collagen genes, such as high levels of Col1a1 and Col1a2 in the neural arches, high levels of Col2a1 in the tesserae, or associated to a drastic Col2a1 downregulation in the centrum. We detect low Col2a1 levels in Xenopus osteoblasts, thereby revealing that the osteoblastic expression of this gene was significantly reduced in the tetrapod lineage. Finally, we uncover a striking parallel, from a molecular and histological perspective, between the vertebral cartilage calcification of both species and discuss the evolutionary origin of endochondral ossification.


Koeppen K.,Institute for Ophthalmic Research | Koeppen K.,Dartmouth College | Reuter P.,Institute for Ophthalmic Research | Ladewig T.,Institute for Ophthalmic Research | And 7 more authors.
Human Mutation | Year: 2010

The CNGA3 gene encodes the A3 subunit of the cone photoreceptor cyclic nucleotide-gated (CNG) channel, an essential component of the phototransduction cascade. Certain mutations in CNGA3 cause autosomal recessive achromatopsia, a retinal disorder characterized by severely reduced visual acuity, lack of color discrimination, photophobia, and nystagmus. We identified three novel mutations in the pore-forming region of CNGA3 (L363P, G367V, and E376K) in patients diagnosed with achromatopsia. We assessed the expression and function of channels with these three new and two previously described mutations (S341P and P372S) in a heterologous HEK293 cell expression system using Western blot, subcellular localization on the basis of immunocytochemistry, calcium imaging, and patch clamp recordings. In this first comparative functional analysis of disease-associated mutations in the pore of a CNG channel, we found impaired surface expression of S341P, L363P, and P372S mutants and reduced macroscopic currents for channels with the mutations S341P, G367V, and E376K. Calcium imaging and patch clamp experiments after incubation at 37°C revealed nonfunctional homo- and heteromeric channels in all five mutants, but incubation at 27°C combined with coexpression of the B3 subunit restored residual function of channels with the mutations S341P, G367V, and E376K. © 2010 Wiley-Liss, Inc.


Elziere L.,Institute for Neurosciences of Montpellier | Sar C.,Institute for Neurosciences of Montpellier | Venteo S.,Institute for Neurosciences of Montpellier | Bourane S.,La Jolla Salk Institute | And 11 more authors.
PLoS ONE | Year: 2014

Neurons innervating peripheral tissues display complex responses to peripheral nerve injury. These include the activation and suppression of a variety of signalling pathways that together influence regenerative growth and result in more or less successful functional recovery. However, these responses can be offset by pathological consequences including neuropathic pain. Calcium signalling plays a major role in the different steps occurring after nerve damage. As part of our studies to unravel the roles of injury-induced molecular changes in dorsal root ganglia (DRG) neurons during their regeneration, we show that the calcium calmodulin kinase CaMK1a is markedly induced in mouse DRG neurons in several models of mechanical peripheral nerve injury, but not by inflammation. Intrathecal injection of NRTN or GDNF significantly prevents the post-traumatic induction of CaMK1a suggesting that interruption of target derived factors might be a starter signal in this de novo induction. Inhibition of CaMK signalling in injured DRG neurons by pharmacological means or treatment with CaMK1a siRNA resulted in decreased velocity of neurite growth in vitro. Altogether, the results suggest that CaMK1a induction is part of the intrinsic regenerative response of DRG neurons to peripheral nerve injury, and is thus a potential target for therapeutic intervention to improve peripheral nerve regeneration. © 2014 Elzière et al.


Maldonado I.L.,Montpellier University Hospital Center | Maldonado I.L.,Institute for Neurosciences of Montpellier | Moritz-Gasser S.,Montpellier University Hospital Center | Moritz-Gasser S.,Institute for Neurosciences of Montpellier | And 2 more authors.
Brain Structure and Function | Year: 2011

Recent diffusion tensor imaging (DTI) tractography studies indicate that the supramarginal gyrus (SMG) represents a relay between frontal and temporal language sites. Some authors postulate that pathways connecting SMG to the posterior temporal lobe, i.e., the posterior part of the superior longitudinal fascicle (SLF) subserve semantic aspects of language. However, DTI provides only anatomic but not functional data. Therefore, it is impossible to conclude. Interestingly, intra-operative electrical mapping of cortical and subcortical language structures during tumor surgery is recognized as a reliable technique in functional neuroanatomy research. We mapped the underlying white matter of the SMG, especially the SLF, in 11 patients who underwent awake surgery for a glioma involving the left inferior parietal lobule. Using direct electrostimulation, we investigated the exact role of the SLF in language. Our findings indicate that the white matter under the inferior parietal lobule is highly involved in the dorsal phonological system. First, the SMG, connected to the ventral premotor cortex by horizontal fibers of the SLF, subserves articulatory processing, as demonstrated by dysarthria elicited by stimulation. Second, long arcuate fibers, found deeper in the white matter, subserve phonological processing, as supported by phonemic paraphasia induced by electrostimulation. Third, the most important result is that no semantic disturbances were elicited by stimulating the SLF, including its posterior part. Furthermore, no semantic disorders occurred postoperatively. Subcortical brain mapping by direct electrical stimulation does not provide arguments for a possible role of the left SLF in language semantic processing. © Springer-Verlag 2011.


Ramirez J.-M.,Montpellier University Hospital Center | Ramirez J.-M.,French Institute of Health and Medical Research | Bai Q.,Montpellier University Hospital Center | Bai Q.,French Institute of Health and Medical Research | And 15 more authors.
Stem Cells and Development | Year: 2013

In culture, human pluripotent stem cells (PSCs) are phenotypically (for instance, the SSEA3 expression level) and functionally (capacity to survive after single-cell dissociation) heterogeneous. We report here that the side scatter (SSC) signal measured by flow cytometry, a variable correlated with membrane irregularity and cell granularity, is very high in PSCs, even higher than in blood polymorphonuclear cells, and markedly heterogeneous. Moreover, SSC intensity rapidly and strongly decreases upon PSC differentiation into any of the three germ layers. PSCs with high SSC (HSSC cells) or low SSC (LSSC cells) values both express pluripotency markers, but HSSC cells are characterized by more frequent simultaneous expression of the membrane pluripotency factors SSEA3, SSEA4, TRA-1-81, TRA-1-60, and CD24 and by a higher mitochondrial content. Functionally, HSSC cells are more likely to generate colonies upon single-cell passage than LSSC cells. SSC monitoring might provide a simple, but robust and rapid method to estimate pluripotency variations in culture and unveils a new phenotypic and functional heterogeneity in PSCs. © 2013 Mary Ann Liebert, Inc.

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