Cytoarchitecture of the olfactory bulb in the laggard mutant mouse.

The laggard (lag) mutant mouse, characterized by hypomyelination and cerebellar ataxia, is a spontaneously occurring mutant mouse caused by mutation in the Kif14 gene. In this mutant mouse, the laminated structures such as the cerebral and cerebellar cortices and the dentate gyrus are cytoarchitecturally abnormal. Macroscopically, the olfactory bulb of the lag mutant mouse is smaller in size and more transparent than the normal counterpart. Hematoxylin-eosin staining reveals that the mutant olfactory bulb has normal lamination in general, but detailed analysis has demonstrated that olfactory periglomerular cells and granule cells are reduced in number. In the mutant, olfactory glomeruli are cytoarchitecturally disorganized and mitral cells are arranged in multiple cell layers instead of being arranged in a single layer. The rostral migratory stream in the mutant becomes gradually thinner or obliterated during early postnatal days. Some of mitral cells and periglomerular cells are multinucleated, suggesting that Kif14 mutation leads to an abnormal cell division. In the mutant, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the subventricular zone of the lateral ventricle are increased in number, especially at perinatal age, suggesting that the decreased population of granule cells in the lag mutant mouse is caused by the increased apoptotic cell death. The olfactory input appears to be intact, as indicated by anterograde labeling of olfactory nerves with an injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the olfactory mucosa. In conclusion, the olfactory bulb of the lag mutant mouse is cytoarchitecturally affected, suggesting that the causal gene for lag mutation, i.e., Kif14, has multiple effects on the development of laminated structures in the central nervous system in addition to the myelin formation.

Branchiogenic motoneurons innervating facial, masticatory, and esophageal muscles show aberrant distribution in the reeler-phenotype mutant rat, Shaking Rat Kawasaki.

Shaking Rat Kawasaki (SRK) is an autosomal recessive mutant rat that is characterized by cerebellar ataxia. Although previous studies indicated many points of similarity between this mutant rat and the reeler mouse, nonlaminated structures such as the facial nucleus have not been studied in this mutant rat. Nissl-stained sections through the brainstem showed that the cytoarchitecture of the facial, motor trigeminal, and ambiguus nuclei was abnormal in SRK, especially in the lateral cell group of the facial nucleus and the compact formation of the ambiguus nucleus. To examine whether orofacial motoneurons are also malpositioned in the SRK rat, horseradish peroxidase (HRP) was injected into the facial, masticatory, and abdominal esophageal muscles of the SRK rats and normal controls to label facial, trigeminal, and ambiguus motoneurons, respectively. HRP-labeled facial, trigeminal, and ambiguus motoneurons of the SRK rat were distributed more widely than those of their normal counterparts, as in the case of the reeler mouse, with the one exception that labeled facial motoneurons innervating the nasolabial muscle were distributed more widely in the ventrolateral-to-dorsomedial direction in comparison with those of the reeler mutant. These data demonstrate that nonlaminated structures in the brainstem of the SRK rat are affected severely, as is the case in the reeler mutant mouse.

Callosal commissural neurons of Dab1 deficient mutant mouse, yotari.

The yotari mouse is an autosomal recessive mutant mouse, caused by mutation of disabled homolog 1 (Dab1) gene. The mutant mouse is recognized by unstable gait and tremor and by early deaths around at the time of weaning. The cytoarchitectures of cerebeller and cerebral cortices and hippocampal formation of the yotari mouse are abnormal. These malformations strikingly resemble those of reeler mouse. In the present study we examined the callosal commissural (CC) neurons of yotari, reeler and normal mice with the injection of recombinant adenovirus into the frontal area 1 (Fr1) to find some possible phenotypes specific for the yotari mouse. The distribution pattern of CC neurons of the yotari was similar to that of the reeler: retrogradely labeled CC neurons were seen throughout all depths of the contralateral Fr1. However, the present statistical analysis revealed that the difference of the mean intracortical position of the CC neurons between the yotari and the reeler is significantly different (Student's t-test), suggesting that the phenotype of the yotari is clearly different from that of the reeler.

[Cytoarchitectonic abnormality in the facial nucleus of the reeler mouse].

Reeler, an autosomal recessive mutant mouse, is characterized by ataxic gait and tremor. In this mutant, the cerebral and cerebellar cortices and hippocampus are cytoarchitectually disorganized: neuronal components are ectopically located in these laminated structures. Since reelin, the gene responsible for the reeler mutation, was discovered by D'Arcangelo et al. (Nature 374: 719-723, 1995), remarkable progress has occurred in this field. The reelin gene encodes an extracellular protein, Reelin, that is crucial for neuronal migration. During embryogenesis, reelin is expressed in the Cajal-Retzius cells in the cerebral cortex and in the outer granule cells in the cerebellar cortex. Although non-laminated structures such as facial nucleus, inferior olivary complex, and dorsal cochlear nucleus are also cytoarchitectually deranged in this mutant, only a few studies have been done to clarify the detailed abnormalities in these non-laminated structures. In this review, we focused on the cytoarchitectonic abnormality in the facial nucleus of the reeler mouse. The branchiomotor neurons in the facial nucleus are generated from the ventricular zone of the floor of the fourth ventricle, migrate ventrolaterally, and finally settle near the ventral surface of the hindbrain. Time schedules for the generation, axon formation and migration of facial motoneurons are similar both in the normal and reeler mice, but the reeler phenotype becomes identifiable at the end of neuronal migration. Although the reason why the facial nucleus is cytoarchitectually abnormal in the reeler mouse is still unknown, the long migration of the facial motoneurons seems to be susceptible to the absence of Reelin in the reeler mouse. In spite of the cytoarchitectual abnormality, retrograde horseradish peroxidase (HRP) study confirmed that the musculotopic arrangements within the facial nucleus of the reeler mouse are still preserved, suggesting that neuronal migration and target recognition are regulated independently. More recently, other reeler-like mutants have been reported. Among them, yotari and scrambler mice arise from mutations in mdab1, a mouse gene related to Drosophila gene disabled (dab). More than 10 years ago, an autosomal recessive rat mutant, shaking rat Kawasaki (SRK), was described that exhibits a phenotype identical to reeler, but the gene responsible for this rat mutation remains unknown. Interestingly, the facial nucleus is cytoarchitectually more deranged in yotari and SRK than their reeler counterpart. Although the reason why yotari exhibits a phenotype identical to reeler in the laminated structures but not in non-laminated structures such as the facial nucleus has remained obscure, mDab1 and Reelin proteins may function as signaling molecules in a different way between laminated and non-laminated structures. Phenotypes resembling that of reeler are seen with mutations in mdab1, cdk5 and p35. Cdk5 and p35 are respectively the catalytic and regulatory subunits of a serine/threonine kinase, that could potentially operate in a common signalling pathway with mDab and Reelin. These plausible partners for Reelin and mDab1 should help us to understand how the activities of these proteins coordinate neuronal migration and rearrangement.

Ambiguus nucleus neurons innervating the abdominal esophagus are malpositioned in the reeler mouse.

To examine whether the migration of ambiguus nucleus (NA) neurons is affected in the reeler mouse, recombinant replication-deficient adenoviral vector carrying E. coli-galactosidase gene (lacZ) was injected into the abdominal esophagus of the reeler mouse and normal control at two months of age prior to 5 days of sacrifice of the animals. In the normal control, lacZ-positive neurons were found in the compact formation of the NA, whereas, in the reeler, they were scattered from the base of the fourth ventricle to the ventro-lateral margin of the medulla. The present study confirmed that NA neurons are malpositioned in the reeler mouse, suggesting that the migration of NA neurons is guided by the reelin-related protein (Reelin).

A case of the bilateral superficial brachial arteries which continued to the radial arteries in the forearms.

During the dissection course of Kobe University School of Medicine, we found the bilateral superficial brachial arteries that continued to the radial arteries in a 90-years-old female cadaver. Each superficial brachial artery is classified Arteria brachialis superficialis lateralis inferior. This artery directly continued to the radial artery in the forearms on each side. Anomalous branching patterns of the (proper) brachial artery in this case belong to the type 7 of Adachi's classification. The incidence and embryological aspects of this anomalous arterial branching are discussed.

Correlation between different types of retinal ganglion cells and their projection pattern in the albino rat.

Injecting Fluoro-Gold (FG) and Evans-Blue (EB) into the right dLGN and SC in the adult albino rat, ipsilaterally projecting double-labeled retinal ganglion cells were mainly seen in the ventrotemporal crescent. They were mainly large sized cells. The ipsilaterally projecting double-labeled cells tended to have larger somata than the single- and double-labeled cells projecting to the contralateral superior colliculus and/or dorsal nucleus of the lateral geniculate body.

Bifurcated projections of retinal ganglion cells bilaterally innervate the lateral geniculate nuclei in the cat.

Cats were injected with the fluorescent retrograde tracers, Fluoro-Gold (FG) and Evans Blue (EB), into the left and right lateral geniculate nuclei (LGN), respectively. About 4.56% of the ganglion cells in the temporal retina were double-labeled by these dyes. 4.7% of these cells were of the large type, 30.3% were of the medium type, and 65% were classified as cells of the small type. These results indicate that members of all three ganglion cell size classes, mainly those of small type, bilaterally innervate the LGN via axonal bifurcation.

The retroesophageal subclavian artery--a case report and review.

In an 80-year-old Japanese male cadaver, the right subclavian artery originated from the aortic arch distal to the origin of the left subclavian artery, i.e., it was the last branch of the aortic arch. It coursed obliquely upwards and to the right behind the esophagus and trachea heading for the superior thoracic aperture. Its area of distribution was normal. Here, we describe this rare anomaly, and discuss its morphologic types, development, incidence, common associated anomalies and clinical correlations.