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Biomedical subjects

Nicolas Tétreault

Publications and source records attributed to Nicolas Tétreault.

5 recordsLinked to original sources
PubMed2006

Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle.

In vertebrates, a limited number of homeobox-containing transcription factors are expressed in the optic vesicle primordium and are required and sufficient for eye formation. At present, little is known about the distinct functions of these factors in optic vesicle growth and on the nature of the main neuroepithelial (NE) progenitor population present in this organ. We have characterized a multipotent cell population present in the mouse optic vesicle that shows extensive proliferation potential and which expresses NE progenitor and retinal markers in vitro. In Pax6 mutant embryos, which form an optic vesicle, we found that the number of resident NE progenitors was greater than normal. In vitro, Pax6-null NE progenitors overproliferate and display reduced p16(Ink4a), p19(Arf), p27(kip1), p57(kip2), and p21(cip1) expression. Pax6 overexpression repressed cellular proliferation and secondary colonies formation, supporting the hypothesis that Pax6 acts cell-autonomously on NE progenitors cell cycle. Notably, these in vitro data correlated with aberrant numbers of mitosis observed in the optic vesicle of early stage Pax6 mutants, with Pax6 association with the chromatin upstream of p27(kip1) promoter region, and with reduced expression levels of p27(kip1), p57(kip2), and p21(cip1) in the primitive forebrain of Pax6 mutants. Taken together, our results suggest that, prior to retinal progenitor cell identity and neurogenesis, Pax6 is required to regulate the proliferation rate of NE progenitors present in the mouse optic vesicle.

Animals↗
PubMed2006

Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.

The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.

Animals↗
PubMed2005

Block copolymers under periodic, strong three-dimensional confinement.

In this communication we study the influence of strong 3D confinement on the self-assembly of diblock copolymers containing a polyferrocenylsilane metallopolymer segment. Both silica colloidal crystals and silica inverse colloidal crystals, having nanometer-scale interconnected pore networks, are used as molds to direct the self-assembly. Unusual morphologies, such as concentric shells and branched lamellae, result from the interaction of the polymer with the high surface area topologically periodic templates.

Journal Article↗
PubMed2004

Characterization of new transcripts enriched in the mouse retina and identification of candidate retinal disease genes.

PURPOSE: Most retinal disease genes are preferentially expressed in photoreceptors, the light-sensitive cells involved in phototransduction. In addition, some of the genes linked to retinal diseases are essential for normal retinal development. The goal of this study was to identify new transcripts enriched in photoreceptors involved in retinal development or diseases. METHODS: To isolate uncharacterized retinal transcripts, the bioinformatic method Digital Differential Display (DDD) was used. RNA in situ hybridization was used to characterize gene-expression patterns. RESULTS: Twenty-seven mouse ESTs highly represented in retinal libraries were identified. Eight ESTs were predominantly expressed in photoreceptors and/or in the retinal pigment epithelium (RPE), whereas transcripts for other ESTs were detected more ubiquitously in the retinal cells or abundantly in ganglion cells and/or the inner nuclear layer. Mapping of the corresponding human orthologues of the photoreceptor/RPE-enriched genes revealed that two of them are candidate disease genes for retinitis pigmentosa, loci RP22 and RP28. Both of these are predominantly expressed in rod photoreceptors. The candidate RP22 gene codes for a putative transmembrane protein showing homology to Cln8 (ceroid lipofuscinosis, neuronal 8), in which gene mutations are associated with photoreceptors degeneration in mice. Also identified were two genes expressed in photoreceptors that are candidate disease genes for recessive Bardet-Biedl syndrome type 3 (BBS3) and recessive ataxia with RP (AXPC1). CONCLUSIONS: This study demonstrates how bioinformatic analysis can be used to identify novel tissue-specific genes relevant to development and diseases.

Animals↗