Biomedical subjects

Susana Nery

Publications and source records attributed to Susana Nery.

8 recordsLinked to original sources

PubMed2006

Cell migration along the lateral cortical stream to the developing basal telencephalic limbic system.

During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial- and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination of in vitro and in vivo approaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomain-containing transcription factor Gsh2 (genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial- and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing gene Gsh2, revealing a novel requirement for Gsh2 in telencephalic development.

Animals↗

PubMed2006

Expression of Plasmodium falciparum genes involved in erythrocyte invasion varies among isolates cultured directly from patients.

Plasmodium falciparum merozoites invade erythrocytes using a range of alternative ligands that includes erythrocyte binding antigenic proteins (EBAs) and reticulocyte binding protein homologues (Rh). Variation in the expression of some of these genes among culture-adapted parasite lines correlates with the use of different erythrocyte receptors. Here, expression profiles of four Rh genes and eba175 are analysed in a sample of 42 isolates cultured from malaria patients in Kenya. The profiles cluster into distinct groups, largely because of very strong negative correlations between the levels of expression of particular gene pairs (Rh1 versus Rh2b, eba175 versus Rh2b, and eba175 versus Rh4), previously associated with alternative invasion pathways in culture-adapted parasite lines. High levels of eba175 are seen in isolates in expression profile group I, and may be associated with sialic acid-dependent invasion. Groups II and III are, respectively, characterized by high levels of Rh2b and Rh4, and are more likely to be associated with sialic acid-independent invasion.

Animals↗

PubMed2005

The temporal and spatial origins of cortical interneurons predict their physiological subtype.

Interneurons of the cerebral cortex represent a heterogeneous population of cells with important roles in network function. At present, little is known about how these neurons are specified in the developing telencephalon. To explore whether this diversity is established in the early progenitor populations, we conducted in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE and CGE, respectively), from which most cortical interneurons arise. Mature interneuron subtypes were assessed by electrophysiological and immunological analysis, as well as by morphological reconstruction. At E13.5, the MGE gives rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP classes distinct from those generated from the E13.5 CGE. Thus, we provide evidence that the spatial and temporal origin of interneuron precursors in the developing telencephalic eminences predicts the intrinsic physiological properties of mature interneurons.

Action Potentials↗

PubMed2005

Notch signaling coordinates the patterning of striatal compartments.

Numerous lines of evidence suggest that Notch signaling plays a pivotal role in controlling the production of neurons from progenitor cells. However, most experiments have relied on gain-of-function approaches because perturbation of Notch signaling results in death prior to the onset of neurogenesis. Here, we examine the requirement for Notch signaling in the development of the striatum through the analysis of different single and compound Notch1 conditional and Notch3 null mutants. We find that normal development of the striatum depends on the presence of appropriate Notch signals in progenitors during a critical window of embryonic development. Early removal of Notch1 prior to neurogenesis alters early-born patch neurons but not late-born matrix neurons in the striatum. We further show that the late-born striatal neurons in these mutants are spared as a result of functional compensation by Notch3. Notably, however, the removal of Notch signaling subsequent to cells leaving the germinal zone has no obvious effect on striatal organization and patterning. These results indicate that Notch signaling is required in neural progenitor cells to control cell fate in the striatum, but is dispensable during subsequent phases of neuronal migration and differentiation.

Animals↗

PubMed2004

Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors.

The Notch and fibroblast growth factor (FGF) pathways both regulate cell fate specification during mammalian neural development. We have shown previously that Notch1 activation in the murine forebrain promotes radial glial identity. This result, together with recent evidence that radial glia can be progenitors, suggested that Notch1 signaling might promote progenitor and radial glial character simultaneously. Consistent with this idea, we found that in addition to promoting radial glial character in vivo, activated Notch1 (ActN1) increased the frequency of embryonic day 14.5 (E14.5) ganglionic eminence (GE) progenitors that grew into neurospheres in FGF2. Constitutive activation of C-promoter binding factor (CBF1), a Notch pathway effector, also increased neurosphere frequency in FGF2, suggesting that the effect of Notch1 on FGF responsiveness is mediated by CBF1. The observation that ActN1 promoted FGF responsiveness in telencephalic progenitors prompted us to examine the effect of FGF pathway activation in vivo. We focused on FGFR2 because it is expressed in radial glia in the GEs where ActN1 increases FGF2 neurosphere frequency, but not in the septum where it does not. Like ActN1, activated FGFR2 (ActFGFR2) promoted radial glial character in vivo. However, unlike ActN1, ActFGFR2 did not enhance neurosphere frequency at E14.5. Additional analysis demonstrated that, unexpectedly, neither ActFGFR2 nor ActFGFR1 could replace the need for ligand in promoting neurosphere proliferation. This study suggests that telencephalic progenitors with radial glial morphology are maintained by interactions between the Notch and FGF pathways, and that the mechanisms by which FGF signaling promotes radial glial character in vivo and progenitor proliferation in vitro can be uncoupled.

Animals↗

PubMed2003

Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches.

To directly test the requirement for hedgehog signaling in the telencephalon from early neurogenesis, we examined conditional null alleles of both the Sonic hedgehog and Smoothened genes. While the removal of Shh signaling in these animals resulted in only minor patterning abnormalities, the number of neural progenitors in both the postnatal subventricular zone and hippocampus was dramatically reduced. In the subventricular zone, this was partially attributable to a marked increase in programmed cell death. Consistent with Hedgehog signaling being required for the maintenance of stem cell niches in the adult brain, progenitors from the subventricular zone of floxed Smo animals formed significantly fewer neurospheres. The loss of hedgehog signaling also resulted in abnormalities in the dentate gyrus and olfactory bulb. Furthermore, stimulation of the hedgehog pathway in the mature brain resulted in elevated proliferation in telencephalic progenitors. These results suggest that hedgehog signaling is required to maintain progenitor cells in the postnatal telencephalon.

Animals↗

PubMed2003

Dlx2 progenitor migration in wild type and Nkx2.1 mutant telencephalon.

The transcription factor Dlx2 is expressed widely throughout the ventral telencephalon. We have examined the in vitro and in vivo migration of Dlx2 progenitors originating from the different ganglionic eminences of both wild type and Nkx2.1 mutant animals. By examining the expression of tauLacZ targeted into the Dlx2 locus we were able to visualize the distribution of cells expressing this gene at both embryonic and postnatal stages. This analysis suggested that Dlx2-expressing cells traverse a number of characteristic migratory routes to populate both cortical and subcortical regions. We also examined how these patterns of migration were affected in Nkx2.1 mutant animals. In these mutants, the early but not late populations of Dlx2-expressing cells originating in the ventral telencephalon that migrate to the cortex are lost. This recovery may be, at least in part, a result of the late migration of Dlx2 progenitors from the caudal ganglionic eminences (CGE), which, based on our previous work, does not appear to require Nkx2.1 gene function.

Animals↗

PubMed2002

The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations.

During development, the mammalian ventral telencephalon is comprised of three major proliferative zones: the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminences. Through gene expression studies, in vitro migration assays, genetic mutant analysis and in vivo fate mapping in mice, we found that the CGE is a progenitor region that is distinct from both the MGE and LGE. Notably, CGE cells showed a unique in vivo pattern of migration, and the CGE contributed cells to nuclei distinct from those populated by the MGE and LGE. Moreover, we report that the migratory fate of cells from the CGE is intrinsically determined by embryonic day 13.5 (E13.5). Together, these results provide the first insights into the development and fate of the CGE.

Animals↗