Time of neuron origin in the diencephalon of the mouse. An autoradiographic study

Time of origin of neurons of thalamus ventralis, thalamus dorsalis, and epithalamus was determined autoradiographically at three transverse levels in adults which received thymidine-H³ once during gestation. A ventrodorsal gradient in the entire region demonstrates a wave of neuron origin in the forebrain, probably rostrocaudal originally but revectored by rearrangement of neuromeres I–III. A caudorostral gradient in dorsal thalamus similarly may represent redirection of an earlier ventrodorsal one. A lateromedial gradient in dorsal thalamus and epithalamus (opposite that in cortex) may reflect lateral displacement of neuroblasts (or their nuclei) by younger elements. Large neurons generally arise before small ones, as seen in epithalamus; the two habenular nuclei illustrate programmed origin of large and small neurons and glia consecutively, with progressively restricted potentiality by the primitive ependyma. Phylogenetically, slight differences in duration of proliferation might radically alter the numbers of small neurons. Although dorsal thalamic nuclei “appear” in external germinal and mantle layers, their neuroblasts originate in primitive ependyma; time of origin accords with subsequent recognition of nuclei and appearance of thalamocortical connections. Massive proliferation (from the 10th to 15th days of gestation) and the gradients overshadow nuclear differences and demonstrate a developmental unity in the dorsal thalamus. The findings further validate Herrick's diencephalic zones and suggest some orderly mechanism, probably at the molecular level, underlying generation of the neurons in this complex brain region.     

Colloid cysts of the third ventricle: ultrastructural features are compatible with endodermal derivation

Summary The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron-lucent cytoplasm and scattered membrane-bound dense-core granules (150–350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium.Presented in part at the Annual Meeting of the American Association of Neuropathologists, Baltimore, MD, June 20–23, 1991     

Development of the preoptic area: time and site of origin, migratory routes, and settling patterns of its neurons

Neurogenesis and morphogenesis in the rat preoptic area were examined with [3H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestational days. Nine groups were exposed to [3H]thymidine on embryonic days E13-E14, E14-E15, E21-E22, respectively. On postnatal day P5, the percentage of labeled cells and the proportion of cells originating during 24-hr periods were quantified at four anteroposterior levels in the preoptic area. Throughout most of the preoptic area there is a lateral to medial neurogenetic gradient. Neurons originate between E12-E15 in the lateral preoptic area, between E13-E16 in the medial preoptic area, between E14-E17 in the medial preoptic nucleus, and between E15-E18 in the periventricular nucleus. These structures also have intrinsic dorsal to ventral neurogenetic gradients. There are two atypical structures: (1) the sexually dimorphic nucleus originates exceptionally late (E15-E19) and is located more lateral to the ventricle than older neurons; (2) in the median preoptic nucleus, where older neurons (E13-E14) are located closer to the third ventricle than younger neurons (E14-E17). For an autoradiographic study of morphogenesis, pregnant females were given a single injection of [3H]thymidine during gestation, and their embryos were removed either two hrs later (short survival) or in successive 24-hr periods (sequential survival). Short-survival autoradiography was used to locate the putative neuroepithelial sources of preoptic nuclei, and sequential survival autoradiography was used to trace the migratory waves of young neurons and their final settling locations. The preoptic neuroepithelium is located anterior to and in the front wall of the optic recess. The neuroepithelium lining the third ventricle is postulated to contain a mosaic of spatiotemporally defined neuroepithelial zones, each containing precursor cells for a specific structure. The neuroepithelial zones and the migratory waves originating from them are illustrated. Throughout most of the preoptic area, neurons migrate predominantly laterally. The older neurons in the lateral preoptic area migrate earlier and settle adjacent to the telencephalon. Younger neurons migrate in successively later waves and accumulate medially. The sexually dimorphic neurons are exceptional since they migrate past older cells to settle in the core of the medial preoptic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chordoid Glioma : A Case Report of Unusual Location and Neuroradiological Characteristics

Since the World Health Organization (WHO) classification for central nervous system neoplasms was declared in 2000, chordoid glioma of the third ventricle has been noted as a newly recognized tumor for central nervous system neoplasms. Although there is not enough universal experience to know the nature of this tumor due to its rarity, the origin of chordoid glioma was guardedly proposed to be the ependymal cells of the third ventricle. Such an idea has been primarily based on the specific location of the tumor, that is, third ventricle, suprasellae, and hypothalamus. However, we report a rare case of histologically confirmed chordoid glioma located in the left thalamus, not attached to any of the midline structures having unusual neuroradiological characteristics.     

Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration

Cell proliferation and migration in the developing mouse olfactory bulb was studied by autoradiography. Animals were injected with thymidine-H³ at various developmental stages and killed one to 96 hours later. All neurons arise in the germinal zone surrounding the ventricle. Until the fourteenth day of gestation (E14) this zone consists only of a matrix (primitive ependymal) layer. From E14 to E17 both matrix and subependymal layers are found, and from E18 to maturity only the subependymal layer is present. The matrix layer produces the mitral cells and some tufted and granule cells; the subependymal layer gives origin to some tufted cells and most of the granule cells. Mitral cell neuroblasts migrate peripherally to reach the primitive mitral cell layer three days after final DNA synthesis. Tufted cell neuroblasts migrate through the developing mitral cell layer to reach their definitive locations; external granule cell neuroblasts migrate past both developing mitral and tufted cells. Neuroglia arise from scattered proliferating glioblasts, originally derived from the periventricular germinal zone. Time of origin and rate of migration of olfactory bulb neurons was checked against the histological development of the bulb. A good agreement corroborated the autoradiographic method used in this study and in previous studies on time of origin of neurons in the central nervous system.     

Bilateral cerebrovascular accidents in incontinentia pigmenti

Choroid plexus papillomas are rare tumors that are confined to areas in which the choroid plexus is normally located. In children, choroid plexus papillomas are predominantly located in the lateral ventricles. Clinically they present with signs of raised intracranial pressure, such as vomiting and increasing head size. Here we report on the clinical, radiologic, and histologic findings of a 4-year-old female who was found to have a tumor in the posterior fossa that had all the histologic hallmarks of a choroid plexus papilloma. This tumor did not originate from the roof of the fourth ventricle as expected but from the ependymal lining covering the median rostral medulla near the pontomedullary junction, a location that so far has not been reported.     

An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat

The dentate gyrus of the rat contains about 600,000 granule cells. These small neurons are generated over a prolonged period from the 14th day of gestation until sime time after the second postnatal week. The majority of the cells pass through their last phase of DNA synthesis in the postnatal period, and during the peak period of cell generation, between the fifth and seventh days after birth, up to 50,000 granule cells are formed each day. Contrary to earlier reports, most of the cells pass through their last mitotic division either within the stratum granulosum itself, or within the hilar region of the developing gyrus. The precursor population of cells in the hilar region must therefore constitute a pool of true neuroblasts. The origin of this pool of cells has not been definitely established but it seems probable that its cells are derived from the neuroepithelium lining the lateral ventricle adjacent to the region from which the hippocampal pyramidal cells are generated. Examination of the final location of granule cells labeled at different stages reveals three distinct morphogenetic gradients in the gyrus. The cells in the dorsal blade tend to be formed earlier than those in the ventral blade; cells in the more caudal (or temporal) portions of the gyrus are generated earlier than those in more rostral (or septal) regions; and in all regions the more superficial neurons in the stratum granulosum are formed earlier than the deeper granule cells. The bearing of some of these findings on the development and organization of the connections of the dentate gyrus is discussed.     

Overexpression of nestin and vimentin in ependymal cells in hydrocephalus

In order to elucidate the immunohistochemical features of hydrocephalic ependyma, immunohistochemical examination was undertaken in 11 normal, post-mortem brains (age range, 11 weeks’ postconception to 6 months after birth) and 12 hydrocephalic brains (three cases each of congenital aqueductal stenosis, Dandy-Walker malformation, Arnold-Chiari type II malformation and posthemorrhagic hydrocephalus) by using antisera to nestin, vimentin and glial fibrillary acidic protein (GFAP). In normal brains, nestin was predominantly expressed in neuroepithelial cells and radial glial fibers during the period of neuronal migration. Vimentin immunoreactivity was principally detected in immature ependymal cells and their basal fibers after the period of neuronal migration, then partly replaced by GFAP reactivity during late gestation. In hydrocephalus, the areas of ependymal disruption were covered with nestin- or vimentin-positive cells. Nestin and vimentin were also expressed in immature ependymal cells or their basal processes in anatomical regions such as the roof or floor plate of the fourth ventricle or the cerebral aqueduct, and the ventral part of the third ventricle. These results suggest that the overexpression of nestin and vimentin in hydrocephalus follows two patterns: a reactive pattern of proliferating immature glial cells associated with ependymal cell loss and an abnormal developmental pattern of immunopositivity associated with anatomical regions in the midline mesencephalon. Received: 27 November 1995 / Accepted: 29 December 1995     

Histogenesis of the cochlear nucleus of the mouse

In Nissl-stained preparations of the cochlear nucleus there are nine recognizable cell types. These cells are born during three periods of histogenesis prenatally. On gestation days 10.0, 10.5, and 11.0 the pyramidal, giant, and dark-staining cells are born. The spherical, globular, multipolar, and horizontal cells are formed on gestation days 12.0, 12.5, and 13.0 and small cells follow on gestation day 14.5. The onset of granule cell formation is gestation day 14.5 and continues to birth on gestation day 19. At birth, and for at least the first 2 postnatal weeks, glial cells are born. There are no regional gradients in cell birth dates, cells from all birth dates being intermixed. Cell birth proceeds in an orderly sequence that is related only to cell size. Although there were no apparent spatiotemporal patterns, some clustering of labeled cells was evident. These observations do not support the hypothesis that Golgi Type I cells precede Golgi Type II cells in their order of birth since both large and small neurons project beyond the nucleus. There is, nonetheless, a sequential pattern in the onset of cell birth for the auditory system, with cochlear nucleus neurons preceding cochlear neurons.     

Origin of colloid cyst: immunoperoxidase study

Despite their consistent anatomic location and histological features, the histogenesis of colloid cysts has remained obscure. We report immunohistochemical data on surgically excised cysts in attempt to define the origin of the lining epithelial cells. Paraffin-embedded tissues from colloidal cysts (7 in the 3rd ventricle and one in the sella) and two similar epithelial cysts (one in the cerebellopontine angle and one in the sella) were investigated. After examination by conventional stains, immunoperoxidase studies were carried out using primary antisera against epithelial membrane antigen (EMA), tissue polypeptide antigen (TPA), epidermal keratin (EK) and S-100 protein. The apical plasma membrane, surface microstructures were consistently EMA positive. Columnar cells demonstrated cytoplasmic staining for TPA. Basal cells of lining epithelia expressed EK. All epithelia studied were negative for S-100 protein. These findings suggest an endodermal origin of colloid cysts.     

Clinicopathological and ultrastructural study in two cases of chordoid glioma

Chordoid glioma is a rare benign neoplasm of uncertain histogenesis occurring in the third ventricle/ /suprasellar region. Recently, data have emerged suggesting that chordoid glioma is a variant of ependymoma related to a specialised ependyma of the subcommisural organ or the lamina terminalis area. In this study, we report clinicopathological and ultrastructural findings in two chordoid glioma cases. In case 1, a tumour (1.5 cm in diameter) in a 62-year-old man invaded the anterior-basal part of the third ventricle in the lamina terminalis region. In case 2, a large tumour in a 51-year-old woman occupied the whole third ventricle. The tumour attached to the medio-basal hypothalamic region. Histologically, both cases revealed a distinct chordoma-like pattern and glial immunophenotype of tumour cells. Under the electron microscope the tumour cells exhibited microvilli, intercellular lumina, intermediate type junctions and focal basal lamina formations. These findings were similar to those previously reported in the chordoid glioma cases. Moreover, the intracytoplasmic cilia and subplasmalemmal pinocytic vesicles or caveoles were observed. The study supports the view of ependymal derivation of chordoid glioma. Its relation to lamina terminalis or infundibular/median eminence area presumably reflecting tumour origin from the modified ependyma of circumventricular organs of the third ventricle is discussed.     

The development of ependyma in the human fetal brain: an immunohistological and electron microscopic study

The stratified inner layer of the embryonic fetal brain, the ventricular zone (VZ), contains glial fibrillary acidic protein (GFAP)-positive cell bodies of radial glia. The adult cerebral ventricle is lined by a single layer of cuboidal, ciliated common ependymal cells which are, immunohistologically, GFAP negative. In late gestation, the ventricular lining is formed by tanycytes, ependymal cells with short, intensely GFAP-positive basal fibres. The development of ependyma was examined, morphologically and immunohistologically, in human fetal brain from between 11 weeks gestation to 6 months post-term to determine the relationship between the radial glia cell, tanycyte and common ependymal cell. This study was not able to show whether tanycytes were formed from radial glia or were formed from a previously uncommitted population of VZ cells. The study did show, however, that tanycytes probably mature into common ependymal cells following acquisition of cilia and loss of basal fibres. Electron microscopic data indicate that tanycytes have features suggestive of a secretory and/or transport function.     

Combined neuroepithelial (colloid) cyst and xanthogranuloma (xanthoma) in the third ventricle.

A case is reported of a combined neuroepithelial cyst and xanthogranuloma of the choroid plexus in the third ventricle of a 22-year-old woman. It is suggested that proliferated neuroepithelial cells lining the cyst enter the fibrous wall through the disrupted basal lamina, and then become xanthomatous cells. Disintegration of these foamy epithelial cells releases lipids and other materials into the cyst wall, provoking a response of macrophages and multinucleated giant cells of foreign-body type. A xanthogranuloma is then formed. The origin of "colloid" cysts is from neuroepithelium; these cysts arise from both ependyma and choroid plexus. Those cysts arising in or near the floor of the third ventricle may originate in stomodeal epithelium, but a distinction cannot be made from neuroepithelial cysts by presently available methods.     

Development of the diencephalon in the rat. III. Ontogeny of the specialized ventricular linings of the hypothalamic third ventricle

The development of the specialized linings of the hypothalamic third ventricle was examined autoradiographically in mature rats that were labelled with ³H-thymidine during the developmental period, and in a closely spaced series of embryonic and infant rats. We distinguished in mature rats, apart from the typical ependymal wall, three specialized linings: the convoluted ependyma, the laminated epithelium, and the tanycytic epithelium. The ventricular wall of most of the anterior hypothalamus, and of the dorsal portion of the posterior hypothalamus, is composed of ciliated ependymal cells and most of them are generated several days before birth, soon after the cessation of neurogenesis in the adjacent hypothalamic nuclei. The cells of the rostral convoluted ependyma adjacent to the paraventricular nucleus are produced at about the same time as the neighboring cells of the smooth ependyma. Its cells come from the same germinal region that we have assumed to generate the neurons of the magnocellular neurohypophysial secretory system. The structural differentiation of the convoluted ependyma starts after birth and is completed by the beginning of the second week. Many of the ependymal cells of the laminated epithelium are produced postnatally, and the production of the specialized cells that form a parallel subependymal row extends into the third week. These cells appear to arise from the same matrix that generates earlier the neurons of the dorsomedial and ventromedial hypothalamic nuclei; their structural differentiation begins during the second week. Also the cells of the tanycytic epithelium are produced mostly postnatally, predominantly during the first week. They appear to arise from the same matrix that generated earlier the neurons of the hypophysiotropic tuberomammillary and arcuate nuclei. It is postulated that these three specialized ventricular linings are specifically related to the three components of the endocrine hypothalamus with which they have shared neuroepithelial sites of origin.     

New ependymal cells are born postnatally in two discrete regions of the mouse brain and support ventricular enlargement in hydrocephalus

A heterogeneous population of ependymal cells lines the brain ventricles. The evidence about the origin and birth dates of these cell populations is scarce. Furthermore, the possibility that mature ependymal cells are born (ependymogenesis) or self-renewed (ependymal proliferation) postnatally is controversial. The present study was designed to investigate both phenomena in wild-type (wt) and hydrocephalic α-SNAP mutant (hyh) mice at different postnatal stages. In wt mice, proliferating cells in the ventricular zone (VZ) were only found in two distinct regions: the dorsal walls of the third ventricle and Sylvian aqueduct (SA). Most proliferating cells were monociliated and nestin+, likely corresponding to radial glial cells. Postnatal cumulative BrdU-labeling showed that most daughter cells remained in the VZ of both regions and they lost nestin-immunoreactivity. Furthermore, some labeled cells became multiciliated and GLUT-1+, indicating they were ependymal cells born postnatally. Postnatal pulse BrdU-labeling and Ki-67 immunostaining further demonstrated the presence of cycling multiciliated ependymal cells. In hydrocephalic mutants, the dorsal walls of the third ventricle and SA expanded enormously and showed neither ependymal disruption nor ventriculostomies. This phenomenon was sustained by an increased ependymogenesis. Consequently, in addition to the physical and geometrical mechanisms traditionally explaining ventricular enlargement in fetal-onset hydrocephalus, we propose that postnatal ependymogenesis could also play a role. Furthermore, as generation of new ependymal cells during postnatal stages was observed in distinct regions of the ventricular walls, such as the roof of the third ventricle, it may be a key mechanism involved in the development of human type 1 interhemispheric cysts.     

Congenital anaplastic ependymoma: a case report of familial glioma

A congenital anaplastic infratentorial ependymoma, occurring in a female infant whose sister also died of brain tumor, is described. The tumor, located in the cerebellum and the fourth ventricle, is characterized by predominantly undifferentiated neuroepithelial cells associated with numerous mitoses, and partially of the cells demonstrating differentiation into ependymal cells and astrocytes. Of special interest is the fact that the elder sister of the patient had also died of a congenital glioma located in the cerebellum and the fourth ventricle, which leads to the discussion about the influences of genetic factors in the development of the familial gliomas as well as about the histogenesis of the tumor examined.     

Neuroblast proliferation on the surface of the adult rat striatal wall after focal ependymal loss by intracerebroventricular injection of neuraminidase

The subventricular zone of the striatal wall of adult rodents is an active neurogenic region for life. Cubic multiciliated ependyma separates the subventricular zone from the cerebrospinal fluid (CSF) and is involved in the control of adult neurogenesis. By injecting neuraminidase from Clostridium perfringens into the right lateral ventricle of the rat, we provoked a partial detachment of the ependyma in the striatal wall. The contralateral ventricle was never affected and was used as the experimental control. Neuraminidase caused widening of the intercellular spaces among some ependymal cells and their subsequent detachment and disintegration in the CSF. Partial ependymal denudation was followed by infiltration of the CSF with macrophages and neutrophils from the local choroid plexus, which ependymal cells never detached after neuraminidase administration. Inflammation extended toward the periventricular parenchyma. The ependymal cells that did not detach and remained in the ventricle wall never proliferated. The lost ependyma was never recovered, and ependymal cells never behaved as neural stem cells. Instead, a scar formed by overlapping astrocytic processes sealed those regions devoid of ependyma. Some ependymal cells at the border of the denudated areas lost contact with the ventricle and became located under the glial layer. Concomitantly with scar formation, some subependymal cells protruded toward the ventricle through the ependymal breaks, proliferated, and formed clusters of rounded ventricular cells that expressed the phenotype of neuroblasts. Ventricular clusters of neuroblasts remained in the ventricle up to 90 days after injection. In the subventricular zone, adult neurogenesis persisted.     

INHERITED PRENATAL HYDROCEPHALUS IN THE H–Tx RAT: A MORPHOLOGICAL STUDY

The H-Tx rat has inherited hydrocephalus which is present at birth. In order to investigate the onset and early stages of hydrocephalus, the heads of fetuses from 16 to 21 days gestation and at 1 day after birth, were serially sectioned using conventional wax histology. Lateral and third ventricle volumes were measured with a graphics tablet and microcomputer. Hydrocephalus was first detected at 18-20 days gestation by enlarged lateral ventricles and it was sometimes accompanied by a large third ventricle. Most hydrocephalics had a non-patent cerebral aqueduct between the third ventricle and the posterior collicular recess and the remainder (about 25%) had an aqueduct which was patent but with a smaller lumen than in non-hydrocephalic littermates. Some fetuses prior to 18 days gestation with normal lateral ventricles also had non-patent aqueducts. Abnormal aqueducts were lined by ependymal cells which were ventrally displaced by thickening of the overlying midbrain; also the subcommissural organ was foreshortened. Infusion with fluorescent markers confirmed that the flow pathway through the aqueduct was obstructed in many hydrocephalic rats. It is concluded that the hydrocephalus may be the result of abnormal brain development in the midline region of the dorsal mesencephalon, leading to aqueduct closure.     

Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricle

The ventral one-third of the ventricular lining in the hypothalamus is formed by specialized ependymal cells called the tanycytes. These cells may serve a neuroendocrine transport function because of their structural specializations, which include apical microvili on the ventricular surface and long basal processes that terminate on blood vessels or on the glia limitans. Here, we describe the expression of mRNA and protein for the glutamate transporters GLT-1 and GLAST in unique tanycyte populations of the third ventricle in rat brain. Using nonisotopic in situ hybridization, we demonstrate GLAST mRNA labeling in tanycytes of the ventral floor and lateral walls in the tuberal and mammillary recess portions of the third ventricle. This GLAST mRNA labeling had a higher intensity than the labeling intensity observed in regular ependymal cells throughout the ventricular system. Furthermore, we have identified strong GLT-1 mRNA labeling in a population of tanycytes situated in the dorsolateral walls of caudal tuberal and mammillary recess portions. Immunocytochemical staining indicates that both GLT-1 and GLAST protein are expressed in the tanycyte populations as well. These data corroborate previous findings that third ventricle tanycytes are functionally heterogeneous. Furthermore, the GLT-1-expressing tanycytes represent a population of tanycytes that, to date, has not been recognized as functionally distinct. The strong GLAST expression by the ventral tanycytes in the hypophysiotropic area suggests a role of tanycyte-mediated glutamate transport in neuroendocrine activity. The functional role of GLT-1 in dorsal wall tanycytes remains to be explored.     

Molecular mapping of the origin of postnatal spinal cord ependymal cells: evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells

Recent studies have suggested that the ependymal cells lining the central canal of postnatal spinal cord possess certain properties of neural stem cells. However, the embryonic origin and developmental potential of the postnatal spinal cord ependymal cells remain to be defined. In this report, we investigated the developmental origin of postnatal spinal ependymal cells by studying the dynamic expression of several neural progenitor genes that are initially expressed in distinct domains of neuroepithelium in young embryos. At later stages of development, as the ventricular zone of the embryonic spinal cord is reduced, expression of Nkx6.1 progenitor gene is constantly detected in ependymal cells throughout chick and mouse development. Expression of other neural progenitor genes that lie either dorsal or ventral to the Nkx6.1+ domain is gradually decreased and eventually disappeared. These results suggest that the remaining neuroepithelial cells at later stages of animal life are derived from the Nkx6.1+ ventral neuroepithelial cells. Expression of Nkx6.1 in the remaining neuroepithelium is closely associated with, and regulated by, Shh expression in the floor plate. In addition, we suggested that the Nkx6.1+ ependymal cells in adult mouse spinal cords may retain the proliferative property of neural stem cells.