To examine the role of the p53 homolog p73 in brain development, we studied p73 Ϫ/Ϫ , p73 ϩ/Ϫ , E2F1 Ϫ/Ϫ , and reeler mutant mice. p73 in developing brain is expressed in Cajal-Retzius (CR) cells, the cortical hem, and the choroid plexus. p73-expressing CR cells are lost in p73 Ϫ/Ϫ embryos, although Reelin is faintly expressed in the marginal zone. Ectopic neurons in the p73 Ϫ/Ϫ preplate and cortical hem at embryonic day 12 implicate p73 in the early developmental program of the cortex; however, preplate partition and early cortical plate formation are not disturbed. Postnatal p73 Ϫ/Ϫ mice show a mild hypoplasia of the rostral cortex and a severely disrupted architecture of the posterior telencephalon. In the developing p73 Ϫ/Ϫ hippocampus, the most striking abnormality is the absence of the hippocampal fissure, suggesting a role of p73 in cortical folding. p73 ϩ/Ϫ mice have a less severe cortical phenotype; they display a dorsal shift of the entorhinal cortex and a reduced size of occipital and posterior temporal areas, which acquire entorhinal-like features such as Reelinpositive cells in layer II. CR cells appear unaffected by heterozygosity. We relate the malformations of the posterior pole in p73 mutant mice to alterations of p73 expression in the cortical hem and suggest that p73 forms part of an early signaling network that controls neocortical and archicortical regionalization. In mice deficient for the transcription factor E2F1, a main activator of the TAp73 (transactivating p73) isoform, we find a defect of the caudal cortical architecture resembling the p73 ϩ/Ϫ phenotype along with reduced TAp73 protein levels and propose that an E2F1-TAp73 dependent pathway is involved in cortical patterning.
Intracortical injections of horseradish peroxidase conjugated with wheat-germ agglutinin (WGA-HRP) reveal a characteristic patchy staining pattern within the superficial layers of cat striate cortex. The patches consist of a dense accumulation of labeled neurons and axonal arborizations. We have investigated the tangential organization and the development of these intrinsic cortical connections by using a flat-mount preparation of area 17. The diameter of the patches varied from 200 to 400 micron, the center-to-center distance ranged from 400 to 800 micron, and the spread of patches extended further in the anterior-posterior than in the medial-lateral direction. The expression of these horizontal patchy connections is age- and experience-dependent. From ten days to six weeks of age patches are exuberant and on occasion fuse to beaded bands extending radially from the injection site. From 6 weeks onwards the number and the tangential spread of the patches decreases to one or two rows of isolated clusters. Long-term binocular deprivation disrupts this pattern of intrinsic connections nearly completely. We infer from these results that there is an inborn pattern of discrete horizontal connections in striate cortex which is shaped by visual experience and requires contour vision for its maintenance.
The expression of ionotropic glutamate receptor subunits in the motoneuronal pools of the hypoglossal nucleus was studied using specific antibodies against subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) subtypes. The highest numbers of intensely immunolabelled motoneurons were found in the dorsal tier and caudoventromedial part of the hypoglossal nucleus with all antibodies except that against the GluR1 AMPA subunit. Labelling for the GluR1 subunit was weak except for caudally located groups of motoneurons which innervate tongue muscles related to respiratory activity. By contrast, most motoneurons were intensely immunostained with antibodies against GluR2/3 and GluR4 subunits of the AMPA subtype. The low staining observed using an antibody specific for the GluR2 subunit (which prevents Ca(2+)-entry through AMPA channels) strongly suggests that AMPA receptors in hypoglossal motoneurons are Ca(2+)-permeable. Immunolabelling for the GluR5/6/7 kainate receptor subunits was found in many motoneuronal somata as well as in thin axon-like profiles and puncta that resembled synaptic boutons. Most motoneurons were intensely immunostained for the NMDA receptor subunit NR1. These results show that the hypoglossal nucleus contains five heterogeneous pools of motoneurons which innervate functionally defined groups of tongue muscles. The uneven expression of the different receptor subunits analysed here could reflect diverse phenotypic properties of hypoglossal motoneurons which might be expected to generate different patterns of motor responses under different physiological or pathological conditions.
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