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S Nery

Publications and source records attributed to S Nery.

7 recordsLinked to original sources

An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development.

The Drosophila Hedgehog protein and its vertebrate counterpart Sonic hedgehog are required for a wide variety of patterning events throughout development. Hedgehog proteins are secreted from cells and undergo autocatalytic cleavage and cholesterol modification to produce a mature signaling domain. This domain of Sonic hedgehog has recently been shown to acquire an N-terminal acyl group in cell culture. We have investigated the in vivo role that such acylation might play in appendage patterning in mouse and Drosophila; in both species Hedgehog proteins define a posterior domain of the limb or wing. A mutant form of Sonic hedgehog that cannot undergo acylation retains significant ability to repattern the mouse limb. However, the corresponding mutation in Drosophila Hedgehog renders it inactive in vivo, although it is normally processed. Furthermore, overexpression of the mutant form has dominant negative effects on Hedgehog signaling. These data suggest that the importance of the N-terminal cysteine of mature Hedgehog in patterning appendages differs between species.

Acylation↗

Telencephalic cells take a tangent: non-radial migration in the mammalian forebrain.

During development of the mammalian telencephalon, cells migrate via diverse pathways to reach their final destinations. In the developing neocortex, projection neurons are generated from cells that migrate radially from the underlying ventricular zone. In contrast, subsets of cells that populate the ventral piriform cortex and olfactory bulb reach these sites by migrating long distances. Additionally, it has been recently established that cells migrate tangentially from the ventral ganglionic eminences to the developing cortex. These tangentially migrating cells are a significant source of cortical interneurons and possibly other cell types such as oligodendrocytes. Here we summarize the known routes of migration in the developing telencephalon, with a particular focus on tangential migration. We also review recent genetic and transplantation studies that have given greater insight into the understanding of these processes and the molecular cues that may guide these migrating cells.

Animals↗

In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain.

Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and final destinations of these neurons in the postnatal brain are not fully understood. Using ultrasound-guided transplantation in utero, we have mapped the migratory pathways and fates of cells born in the lateral and medial ganglionic eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE and MGE cells migrate along different routes to populate distinct regions in the developing brain. We show that LGE cells migrate ventrally and anteriorly, and give rise to the projecting medium spiny neurons in the striatum, nucleus accumbens and olfactory tubercle, and to granule and periglomerular cells in the olfactory bulb. By contrast, we show that the MGE is a major source of neurons migrating dorsally and invading the developing neocortex. MGE cells migrate into the neocortex via the neocortical subventricular zone and differentiate into the transient subpial granule neurons in the marginal zone and into a stable population of GABA-, parvalbumin- or somatostatin-expressing interneurons throughout the cortical plate.

Animals↗

Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain.

This study addresses the role of Sonic hedgehog (Shh) in promoting the generation of oligodendrocytes in the mouse telencephalon. We show that in the forebrain, expression of the early oligodendrocyte markers Olig2, plp/dm20 and PDGFR(alpha) corresponds to regions of Shh expression. To directly test if Shh can induce the development of oligodendrocytes within the telencephalon, we use retroviral vectors to ectopically express Shh within the mouse embryonic telencephalon. We find that infections with Shh-expressing retrovirus at embryonic day 9.5, result in ectopic Olig2 and PDGFR(alpha) expression by mid-embryogenesis. By postnatal day 21, cells expressing ectopic Shh overwhelmingly adopt an oligodendrocyte identity. To determine if the loss of telencephalic Shh correspondingly results in the loss of oligodendrocyte production, we studied Nkx2.1 mutant mice in which telencephalic expression of Shh is selectively lost. In accordance with Shh playing a role in oligodendrogenesis, within the medial ganglionic eminence of Nkx2.1 mutants, the early expression of PDGFR(alpha) is absent and the level of Olig2 expression is diminished in this region. In addition, in these same mutants, expression of both Shh and plp/dm20 is lost in the hypothalamus. Notably, in the prospective amygdala region where Shh expression persists in the Nkx2.1 mutant, the presence of plp/dm20 is unperturbed. Further supporting the idea that Shh is required for the in vivo establishment of early oligodendrocyte populations, expression of PDGFR(alpha) can be partially rescued by virally mediated expression of Shh in the Nkx2.1 mutant telencephalon. Interestingly, despite the apparent requirement for Shh for oligodendrocyte specification in vivo, all regions of either wild-type or Nkx2.1 mutant telencephalon are competent to produce oligodendrocytes in vitro. Furthermore, analysis of CNS tissue from Shh null animals definitively shows that, in vitro, Shh is not required for the generation of oligodendrocytes. We propose that oligodendrocyte specification is negatively regulated in vivo and that Shh generates oligodendrocytes by overcoming this inhibition. Furthermore, it appears that a Shh-independent pathway for generating oligodendrocytes exists.

Animals↗

On the role of the general transcription factor Sp1 in the activation and repression of diverse mammalian oxidative phosphorylation genes.

To gain insight into the role of the general transcription factor, Sp1, in the expression of nuclear genes involved in mitochondrial biogenesis, we investigated Sp1 activation of the adenine nucleotide translocator 2, cytochrome c1, F1-ATPase beta subunit, and the mitochondria transcription factor (mtTFA) promoters transfected into Drosophila cell lines. The numbers and organization of GC elements vary in the four promoters, but the magnitude of activation by coexpressed human Sp1 was similar. A feature common to the four promoters is the presence of multiple, proximal Sp1-activating elements that account for 50% or more of the transcription activation by Sp1. The distribution and function of individual distal Sp1 elements is less defined and appear to be more promoter-specific. Finally, data from transfected Drosophila cells provide the first direct proof for the involvement of Sp1 in the negative regulation of the ANT2 promoter and as a possible participant in repression of the beta-subunit promoter. The role of Sp1 in both the positive and negative regulation of OXPHOS promoters is unique.

Animals↗

A comparative study of three dental adhesives.

The shear bond strengths of three dental adhesives to dentine and a NiCrBe alloy were determined. Forty human third permanent molar teeth were ground to expose superficial dentine, to 20 of which P50 composite was bonded, using All-Bond 2 (n = 10) or Scotchbond 2 (n = 10). Alloy discs were bonded to the remaining 20 specimens, using either All-Bond 2 (n = 10) or Panavia Ex (n = 10). All specimens were stored at 37 degrees C. 100% RH, for 24 h. Testing was carried out using a shear jig at a cross-head speed of 1 mm min-1, following which a 0.5 mm increment was removed to expose middle dentine for further bond tests (n = 10 for each adhesive). Removal of a further 0.5 mm increment exposed 'deep' dentine for final dentine bond strength tests. Results were then aggregated for each substrate/adhesive combination (n = 30). Alloy/alloy bond strengths were determined after bonding alloy discs together using Panavia Ex (n = 30) or All-Bond 2 (n = 30). Results were analysed using ANOVA and Weibull analysis. All-Bond 2 produced significantly greater and more reliable bond strengths to dentine than did either Scotchbond 2 or Panavia Ex. The bond strength of Scotchbond 2 and Panavia Ex to dentine was dependent upon the dentine depth whereas the bond strength of All-Bond 2 to dentine was independent of dentine depth. Alloy/alloy bond strengths were significantly greater when using Panavia Ex compared with All-Bond 2.

Acid Etching, Dental↗