Biomedical subjects

Jonas Frisén

Publications and source records attributed to Jonas Frisén.

9 recordsLinked to original sources

PubMed2003

Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map.

Olfactory sensory neurons expressing a given odorant receptor (OR) project with precision to specific glomeruli in the olfactory bulb, generating a topographic map. In this study, we demonstrate that neurons expressing different ORs express different levels of ephrin-A protein on their axons. Moreover, alterations in the level of ephrin-A alter the glomerular map. Deletion of the ephrin-A5 and ephrin-A3 genes posteriorizes the glomerular locations for neurons expressing either the P2 or SR1 receptor, whereas overexpression of ephrin-A5 in P2 neurons results in an anterior shift in their glomeruli. Thus the ephrin-As are differentially expressed in distinct subpopulations of neurons and are likely to participate, along with the ORs, as one of a complement of guidance receptors governing the targeting of like axons to precise locations in the olfactory bulb.

Animals↗

PubMed2003

Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes.

The mechanisms generating precise connections between specific thalamic nuclei and cortical areas remain poorly understood. Using axon tracing analysis of ephrin/Eph mutant mice, we provide in vivo evidence that Eph receptors in the thalamus and ephrins in the cortex control intra-areal topographic mapping of thalamocortical (TC) axons. In addition, we show that the same ephrin/Eph genes unexpectedly control the inter-areal specificity of TC projections through the early topographic sorting of TC axons in an intermediate target, the ventral telencephalon. Our results constitute the first identification of guidance cues involved in inter-areal specificity of TC projections and demonstrate that the same set of mapping labels is used differentially for the generation of topographic specificity of TC projections between and within individual cortical areas.

Animals↗

PubMed2003

Blood on the tracks: a simple twist of fate?

Recent studies suggest that non-neural cells can generate neurons in mice and humans. There is no lack of excitement about these results: they challenge our view of cellular differentiation and the prospect of being able to generate neurons from, for example, blood is very attractive. But is it too good to be true?

Animals↗

PubMed2002

Embryonic stem cells: taming the fountain of youth.

Embryonic stem cells readily generate neurons in vitro, but steering their differentiation into specific neuronal subtypes is a major challenge. It has now been shown that mechanisms that regulate neuronal specification during development can be applied to embryonic stem cells in vitro; this may lead to new ways of generating cells for therapy.

Animals↗

PubMed2002

Amphiregulin is a mitogen for adult neural stem cells.

Neurons are continuously generated from stem cells in the hippocampus and along the lateral ventricles in the adult brain. Neural stem cells can be propagated in vitro in the presence of epidermal growth factor (EGF) or fibroblast growth factor-2. We report here that amphiregulin, a growth factor related to EGF, is a mitogen for adult mouse neural stem cells in vitro and displays potency similar to that of EGF. Neural stem cell cultures can be initiated and the cells propagated as efficiently in the presence of amphiregulin only as with EGF. Furthermore, we show that amphiregulin is expressed in the choroid plexus of the ventricular system and in the hippocampus in the adult brain, suggesting that amphiregulin may participate in the regulation of neural stem cell proliferation and neurogenesis in the adult brain.

Age Factors↗

PubMed2002

Gene delivery to adult neural stem cells.

Neural stem cells may present an ideal route for gene therapy as well as offer new possibilities for the replacement of neurons lost to injury or disease. However, it has proved difficult to express ectopic genes in stem cells. We report methods to introduce genes into adult neural stem cells using viral and nonviral vectors in vitro and in vivo. Adenoviral and VSV-G-pseudotyped retroviral vectors are more efficient than plasmid transfection or VSV-G lentiviral transduction in vitro. We further show that adult neural stem cells can be directed to a neuronal fate by ectopic expression of neurogenin 2 in vitro. Plasmids can be delivered in vivo when complexed with linear polyethyleneimine, and gene expression can be targeted specifically to neural stem or progenitor cells by the use of specific promoters. These techniques may be utilized both to study the function of various genes in the differentiation of neural stem cells to specific cell fates and, ultimately, for gene therapy or to generate specific differentiated progeny for cell transplantation.

Adenoviridae↗

PubMed2002

Stem cell plasticity?

Cells differentiate according to stereotype pedigrees, or at least so we thought. Several studies have challenged this dogma and suggested that stem cells in several tissues may be plastic and switch lineages, but many of the results are open to other interpretations. Is there solid evidence for stem cell plasticity and should we rewrite the textbooks just yet?

Animals↗

PubMed2002

Functional integration of adult-born neurons.

Over the past decade, it has become clear that neural stem cells in the adult mammalian brain continuously generate new neurons, predominantly in the hippocampus and olfactory bulb. However, the central issue of whether these new neurons participate in functional synaptic circuitry has yet to be resolved. Here, we use virus-based transsynaptic neuronal tracing and c-Fos mapping of odor-induced neuronal activity to demonstrate that neurons generated in the adult functionally integrate into the synaptic circuitry of the brain.

Animals↗

PubMed2002

Ephrins are not only unattractive.

The ephrins and their Eph receptors have emerged as repulsive cues for growing axons during the past decade. Since then, great effort has been made to understand the significance and mechanisms of Eph-mediated repulsion. More recently, it has become clear that ephrins perform in many more developmental processes than the repulsion-dependent establishment of topography in the nervous system. As numerous studies suggest functions more akin to adhesion or attraction than to repulsion, increasing attention is now being paid to the intracellular mechanisms that might explain this duality.

Animals↗