Search PubMed⌕ Search

Biomedical subjects

H Cremer

Publications and source records attributed to H Cremer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lamina-specific cell adhesion on living slices of hippocampus.

Laminar distribution of fiber systems is a characteristic feature of hippocampal organization. Ingrowing afferents, e.g. the fibers from the entorhinal cortex, terminate in specific layers, which implies the existence of laminar recognition cues. To identify cues that are involved in the laminar segregation of fiber systems in the hippocampus, we used an in vitro assay to study the adhesion of dissociated entorhinal cells on living hippocampal slices. Here we demonstrate that dissociated entorhinal cells adhere to living hippocampal slices with a lamina-specific distribution that reflects the innervation pattern of the entorhino-hippocampal projection. In contrast, laminae which are not invaded by entorhinal fibers are a poor substrate for cell adhesion. Lamina-specific cell adhesion does not require the neural cell adhesion molecule or the extracellular matrix glycoprotein reelin, as revealed in studies with mutants. However, the pattern of adhesive cues in the reeler mouse hippocampus mimics characteristic alterations of the entorhinal projection in this mutant, suggesting a role of layer-specific adhesive cues in the pathfinding of entorhinal fibers. Lamina-specific cell adhesion is independent of divalent cations, is abolished after cryofixation or paraformaldehyde fixation and is recognized across species. By using a novel membrane adhesion assay, we show that lamina-specific cell adhesion can be mimicked by membrane-coated fluorescent microspheres. Recognition of the adhesive properties of different hippocampal laminae by growing axons, as either a growth permissive or a non-permissive substrate, may provide a developmental mechanism underlying the segregation of lamina-specific fiber projections.

Afferent Pathways↗
PubMed1998

[Measles].

Explore the source record for details and available documents.

Child↗
PubMed1997

VASE-encoded peptide modifies NCAM- and L1-mediated neurite outgrowth.

Interactions between the neural cell adhesion molecule (NCAM) with NCAM-expressing neurons (trans-interaction) stimulate outgrowth of neurites. The extent of NCAM-triggered neurite outgrowth depends on the presence of 10 amino acids derived from the variable alternatively spliced exon (VASE or pi-exon) in the fourth immunoglobulin-like domain of NCAM (Ig4): NCAM with VASE reduces and without VASE enhances neurite outgrowth in cis- or trans-interaction. We have investigated the role of VASE in neurite outgrowth by characterizing the receptors at the cell surface of cultured cerebellar neurons. Results from experiments with L1 and NCAM antibodies and with cerebellar neurons derived from wild-type or NCAM-deficient mice show that substrate-coated Ig4 with VASE (Ig4+) or without VASE (Ig4-) stimulates neurite outgrowth by a trans-interaction with L1 and that Ig4- promotes neurite outgrowth more strongly than Ig4+ by a transinteraction with NCAM.

Alternative Splicing↗
PubMed1997

NCAM is essential for axonal growth and fasciculation in the hippocampus.

The neural cell adhesion molecule (NCAM), probably the best characterized and most abundant cell adhesion molecule on neurons, is thought to be a major regulator of axonal growth and pathfinding. Here we present a detailed analysis of these processes in mice deficient for all NCAM isoforms, generated by gene targeting. The hippocampal mossy fiber tract shows prominent expression of polysialylated NCAM and the generation of new axonal projections throughout life. Focusing on this important intrahippocampal connection, we demonstrate that in the absence of NCAM, fasciculation and pathfinding of these axons are strongly affected. In addition we show alterations in the distribution of mossy fiber terminals. The phenotype is more severe in adult than in young animals, suggesting an essential role for NCAM in the maintenance of plasticity in the mature nervous system.

Aging↗
PubMed1997

Absence of the myelin-associated glycoprotein (MAG) and the neural cell adhesion molecule (N-CAM) interferes with the maintenance, but not with the formation of peripheral myelin.

We have previously shown that mice deficient in the gene for the myelin-associated glycoprotein (MAG) develop normal myelin in the peripheral nerves, but show axon and myelin degeneration at eight months of age, suggesting that MAG is involved in the maintenance of axon-Schwann cell integrity. The search for molecules that might replace MAG during myelination revealed an overexpression of the neural cell adhesion molecule (N-CAM) at those aspects where MAG is detectable in wild type mice. To test whether N-CAM might compensate for MAG during myelination in MAG-deficient mice, double mutants deficient in both MAG and N-CAM (MAG-/N-CAM- mice) were generated by cross-breeding the single mutants. Whereas alterations of myelin development were not detectable in either of the single or double mutants, degeneration of myelin and axons occurred approximately 4 weeks earlier in MAG-/N-CAM- than in MAG- mutants. Furthermore, at 8 weeks of age, single fiber preparation and electron microscopy revealed that the number of profiles indicative of degeneration was substantially increased in MAG-/N-CAM- mutants when compared to MAG- mice. These data suggest that in MAG-deficient mice N-CAM does not compensate for MAG in myelin formation but partially substitutes for it in the maintenance of axon-myelin integrity.

Animals↗
PubMed1997

Defects in sensory and autonomic ganglia and absence of locus coeruleus in mice deficient for the homeobox gene Phox2a.

Phox2a is a vertebrate homeodomain protein expressed in subsets of differentiating neurons. Here, we show that it is essential for proper development of the locus coeruleus, a subset of sympathetic and parasympathetic ganglia and the VIIth, IXth, and Xth cranial sensory ganglia. In the sensory ganglia, we have identified two differentiation blocks in Phox2a-/- mice. First, the transient expression of dopamine-beta-hydroxylase in neuroblasts is abolished, providing evidence that Phox2a controls noradrenergic traits in vivo. Second, the expression of the GDNF receptor subunit Ret is dramatically reduced, and there is a massive increase in apoptosis of ganglion cells, which are known to depend on GDNF in vivo. Therefore, Phox2a appears to regulate conventional differentiation traits and the ability of neurons to respond to essential survival factors.

Animals↗
PubMed1997

Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM).

Mice deficient for the neural cell adhesion molecule (NCAM) show morphological and behavioural abnormalities in the adult form, including a reduced size of the olfactory bulb, reduced exploratory behaviour, and deficits in spatial learning. Here we report increased aggressive behaviour of both homozygous (NCAM -/-) and heterozygous (NCAM +/-) male mutant mice towards an unfamiliar male intruding into their home cage. While plasma testosterone concentrations did not differ between genotypes before or after behavioural testing, corticosterone levels were higher in mutant residents than in wild-type (NCAM +/+) residents 30 min after encountering the intruder. Levels of c-fos mRNA, analysed to monitor neuronal activation, were similar in primary output structures of the olfactory bulb in NCAM-deficient and NCAM +/+ mice, but were increased in brain areas of the limbic system in both NCAM -/- and NCAM +/- mutant mice after the behavioural test. These results indicate that abnormalities in social behaviour correlate with enhanced neuronal activity in limbic brain areas and result in increased social stress in NCAM-deficient mice.

Aggression↗
PubMed1997

Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis.

Recent evidence suggests that specific families of homeodomain transcription factors control the generation and survival of distinct neuronal types. We had previously characterized the homeobox gene Phox2a, which is expressed in differentiating neurons of the central and peripheral autonomic nervous system as well as in motor nuclei of the hindbrain. Targeted deletion of the Phox2a gene affects part of the structures in which it is expressed: the locus coeruleus, visceral sensory and parasympathetic ganglia and, as we show here, the nuclei of the IIIrd and IVth cranial nerves. We now report on the characterization of Phox2b, a close relative of Phox2a, with an identical homeodomain. Phox2a and Phox2b are co-expressed at most sites, therefore suggesting a broader role for Phox2 genes in the specification of the autonomic nervous system and cranial motor nuclei than revealed by the Phox2a knock-out mice. A detailed analysis of the relative timing of Phox2a and Phox2b expression at various sites suggests positive cross-regulations, which are substantiated by the loss of Phox2b expression in cranial ganglia of Phox2a-deficient mice. In the major part of the rhombencephalon, Phox2b expression precedes that of Phox2a and starts in the proliferative neuroepithelium, in a pattern strikingly restricted on the dorsoventral axis and at rhombomeric borders. This suggests that Phox2b links early patterning events to the differentiation of defined neuronal populations in the hindbrain.

Amino Acid Sequence↗
PubMed1996

Bequests as a heir "disciple device.".

"This paper develops a model of inter vivos gifts and bequests in a setting of moral hazard and adverse selection. Altruistic parents do not perfectly know how much effort their children make to earn their living, nor do they know their true level of ability. Inter vivos gifts take place prior to the realization of the children's earnings whereas at the moment of bequests, parents do observe them. We show that an optimal transfer policy generally uses a mix of inter vivos gifts--deemed as more efficient--and bequests--deemed as more redistributive."

Economics↗
PubMed1996

PSA-NCAM is required for activity-induced synaptic plasticity.

Hippocampal organotypic slice cultures maintained 10-20 days in vitro express a high level of the polysialylated embryonic form of neural cell adhesion molecule (NCAM) (PSA-NCAM). Treatment of the cultures with endoneuraminidase-N selectively removed polysialic acid (PSA) from NCAM and completely prevented induction of long-term potentiation (LTP) and long-term depression (LTD) without affecting cellular or synaptic parameters. Similarly, slices prepared from transgenic mice lacking the NCAM gene exhibited a decaying LTP. No inhibition of N-methyl-D-aspartic acid receptor-dependent synaptic responses was detected. Washout of the enzyme resulted in reexpression of PSA immunoreactivity which correlated with a complete recovery of LTP and LTD. This reexpression was blocked by TTX and low calcium and enhanced by bicuculline. Taken together, these results indicate that neuronal activity regulates the expression of PSA-NCAM at the synapse and that this expression is required for the induction of synaptic plasticity.

Animals↗
PubMed1996

Use of chimeric F3-NCAM molecules to explore the properties of VASE exon in modulating polysialylation and neurite outgrowth.

Differential splicing of VASE exon in the fourth immunoglobulin (Ig) domain and attachment to the fifth Ig domain of alpha 2-8 linked sialic acid (PSA) both dramatically change, in opposite manner, Neural Cell Adhesion Molecule (NCAM) functional properties. Reciprocal patterns of VASE and PSA expression suggest that they might be mutually exclusive. Here, we tested whether informations conferring polysialylation reside in NCAM-Ig domains 4 and 5 and the influence of the VASE exon encoded sequence on this process. We also examined if the VASE sequence was still able to inhibit neurite outgrowth when presented out of its normal NCAM context. Constructs have been prepared encoding NCAM-Ig domains 4 (with or without the VASE exon) and 5 fused to the F3 molecule. Stable clones expressing the chimeric molecules or wild type F3 were then obtained in the AtT-20 cell line. Although the chimeric molecules were expressed on the cell surface none of them was bearing PSA. Thus, polysialylation cannot be conferred to proteins by addition of the NCAM-Ig domains 4 and 5 modular motif and in this molecular context, the VASE sequence is not influencing the process. These chimeric molecules, either expressed at the surface of RIN or COS cells or presented as soluble forms, were examined for their effect on neurite outgrowth. In all cases, the length of neurites of sensory neurons was significantly reduced when grown in presence of the VASE containing chimera by comparison with the chimera without VASE or wild type F3. When neurons from NCAM knock-out mice were used for the assay, the VASE inhibition could not be detected. Thus VASE is able to act as a modular motif and NCAM expressed on neurons participates in transducing its effect.

Animals↗