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PubMed1979

Gliogenesis and ependymogenesis during embryonic development of the rat. An autoradiographic study.

With the aid of [3H]thymidine autoradiography gliogenesis and ependymogenesis were studied in the brain of the rat during embryonic development. Gliogenesis was found to begin on day 17 of gestation in the caudal regions of the brain stem, and to spread rostrally. On days 20 and 21 of gestation gliogenesis reached a peak, and then declined. Ependymogenesis began earlier and showed the following pattern: day 14 of gestation in the 4th ventricle and cerebral aqueduct, day 15 in the 3rd ventricle, and day 17 in the lateral ventricles reaching a peak on different days in different sites. Both gliogenesis and ependymogensis continued up to the last day of gestation, day 22. Issues pertaining to gliogenesis and the formation of glioblasts, and the relationship between gliogenesis and ependymogenesis are discussed.

Animals↗
PubMed1977

Gliogenesis during embryonic development in the rat.

With the aid of thymidine-H3 autoradiography gliogenesis in the rat brain was seen to start during embryonic stages, which might continue into the postnatal stages of development. Gliogenesis followed a caudo-rostral gradient closely following neurogenesis. Ependymogenesis was found to occur in parallel with gliogenesis.

Animals↗
PubMed2024

A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex.

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascl1, Egfr, and Olig2. The increased Ascl1 expression and appearance of Egfr+ and Olig2+ cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.

Animals↗
PubMed1978

Testing of the course of neurogenesis and gliogenesis in the germinative zones of the CNS of embryonal and early postnatal rats by means of the gel reaction for the histochemical demonstration of the thiamine-pyrophosphatase. Histochemical and autoradiographical study.

Using the histochemical reaction for the demonstration of TPPase the shape and distribution of the Golgi apparatus (GA) of the ventricular zones of the CNS of rats was studied during embryonal and postnatal development. In the cells of the ventricular zone of the spinal cord, the Hypothalamus, the Thalamus, the N. caudatus and the Cerebral cortex two forms of GA can be distinguished: Form 1 GA has the shape of small rods or grains placed in the ventricular process of the cell at various distances from the nucleus. In the spinal cord and the Hypothalamus the 1st form correlates with the period of neuroblastic production, and the same correlation probably exists in other regions of the CNS also. Form 2 GA is in sequence with form 1; it is characterized by a large beam shape, situated supranuclearly near to the nucleus. The relation of form 2 to gliogenesis is discussed. In the alar region of the spinal cord only form 1 GA occurs. The GA of cells of the subventricular zone has on average a lower enzymatic activity than that of the ventricular zone. By day 18 intra uterinam the subventricular cells have the shape of very small grains (1 micron) or are not visible. From day 18 intra uterinam cells with a large GA begin to appear and steadily grow in number until postnatally they form the majority of the subventricular layer. Autoradiographical investigation and a comparison with published data showed that cells without GA and with discrete GA are stem cells and those with a large GA are glioblasts. Glioblasts are arranged in the subventricular zone with the GA pointing in the direction of migration. According to the ratio of glioblasts and stem cells topographical regions can be divided into early, transitional and permanent phases of glioproduction. The gel method of demonstrating TPPase is highly suitable for study of the differentiation of the CNS and for observing the progress of glioproduction.

Animals↗
PubMed1978

Radioautographic investigation of gliogenesis in the corpus callosum of young rats. I. Sequential changes in oligodendrocytes.

The corpus callosum of young rats was examined to clarify the behavior of the three subtypes of oligodendrocytes (the large organelle-rich "light oligodendrocytes," the smaller and more densely stained cells referred to as "medium oligodendrocytes," and the even smaller and denser "dark oligodendrocytes"). It was hoped to find out whether cells of the three subtypes undergo division and how they are related to one another. 3H-thymidine was given intraperitoneally as single or three shortly spaced injections to a first group of 19- to 20-day old rats weighing about 40 g, and to a second group of 25-day old rats weighing about 80 g. The animals were sacrificed at various time intervals from 2 hours to 35 days after 3H-thymidine administration. Pieces of corpus callosum were taken near the superior lateral angle of the lateral ventricles; and semithin sections were radioautographed and stained with toluidine blue. Two hours after 3H-thymidine injection, label is virtually absent from light, medium and dark oligodendrocytes, from microglia, and probably from astrocytes, but is present in about 10% of the immature glial cells, which include the poorly differentiated glioblasts and the partially differentiated oligodendroblasts and astroblasts. Hence, the cells undergoing DNA synthesis and mitosis in the corpus callosum are these three types of immature cells. During the week that follow the administration of 3H-thymidine, label appears in oligodendrocytes and astrocytes, which presumably have arisen from the initially labeled immature cells. The oligodendrocytes acquire label in a sequential manner: the light cells show label first and their labeling index reaches a peak at the seven-day interval; the medium oligodendrocytes become labeled next with a labeling peak toward the 14- and 21-day intervals and, finally, the dark oligodendrocytes with a peak around the 28-day interval. Analysis by the method of Zilversmit et al. ('42-'43) provides precise details on the sequence: immature cells presumed to be oligodendroblasts give rise to light oligodendrocytes which, after four to seven days, transform into medium oligodendrocytes which, after another 11 to 18 days, transform into dark oligodendrocytes. The dark cells may persist indefinitely or turn over at a very slow rate. It is concluded that oligodendrocytes arise from the last division of oligodendroblasts and develop in three main periods: a light stage lasting less than a week, a medium stage lasting about two weeks, and a very long lasting dark stage.

Animals↗
PubMed1978

Radioautographic investigation of gliogenesis in the corpus callosum of young rats. II. Origin of microglial cells.

Microglial cells are absent from the corpus callosum of newborn rats. In the hope of finding out when and how microglial cells appear with age, 3H-thymidine was given intraperitoneally as single or three shortly spaced injections to 5-day-old rats weighing about 15 g; and these animals were sacrificed at various time intervals from 2 hours to 35 days later. Pieces of corpus callosum were taken near the superior lateral angle of the lateral ventricles; and semithin sections were radioautographed and stained with toluidine blue. The corpus callosum of 5-day-old rats is composed of loosely arranged unmyelinated fibers and scattered cells. Among these cells, microglia are rare; there are a few astrocytes, many immature glial cells, rare pericytes, and 6--7% of phagocytic "ameboid cells" consisting of a few monocytes and many macrophages. In the animals sacrificed two hours after 3H-thymidine administration, label is present only in immature cells and "ameboid cells." As time elapses and the fibers of corpus callosum become myelinated, oligodendrocytes and, later, microglial cells appear. At the age of 12 days, microglial cells are present in substantial number; and by 19 days, the number doubles to reach a plateau. Many of the new microglial cells are labeled, e.g., 78.1% in 12-day-old animals (7 days after 3H-thymidine administration). The labeled microglial cells must have come from the transformation of cells that acquired label early, that is, from the immature cells or the "ameboid cells." The height of the peaks of labeling--59.8% at nine days for immature cells and 77.8% at 12 days for "ameboid cells"--points to the latter as precursors of the highly labeled microglial cells. Furthermore, the "ameboid cells" disappear as microglial cells appear and there are transitional elements between these two cell types. Cell counts suggest that about a third of the "ameboid cells" transform into microglial cells, while the others degenerate and die. Thus, the microglial cells which appear in the corpus callosum during the first three weeks of life result from transformation of the "ameboid cells"--a group of macrophages showing various stages of transition from monocytes. As for the occasional microglial cell appearing after the third week or in the adult, they presumably come directly from monocytes. In either case, monocytes would be the initial precursors.

Aging↗
PubMed1979

Cell death and optic fiber penetration in the optic stalk of the chick.

The role of dying cells in the optic stalk in relation to retinal fiber migration was investigated in the chick embryo. Cell death was analysed at various stages of development by counting pycnotic nuclei and also by the Gomori acid phosphatase reaction, while nerve fibers were visualised by the Bodian method. A wave of cell death, beginning in the neural retina at stage 18 and advancing with time through the stalk towards the diencephalon, occurred simultaneously or slightly prior to differentiation and migration of ganglion cell axons. Cell death stopped and gliogenesis occurred in the stalk after penetration by retinal fibers. Cell death occurred in the stalk even when fiber penetration was prevented by optic cup ablation. In this case, necrosis ensued until almost complete degeneration of the stalk, usually within three days after the operation, and gliogenesis did not occur. As the stalk degenerated, its cells became heavily pigmented. These observations suggest that the onset of cell death in the optic stalk is determined prior to and independently of retinal fiber penetration. On the other hand, cessation of cell death and subsequent gliogenesis occur only in the presence of ingrowing optic fibers.

Acid Phosphatase↗
PubMed2026

Tailless terminates the neural stem cell temporal cascade in both the optic lobe and central brain.

Temporal patterning is an evolutionarily conserved mechanism to produce neuronal and glial diversity from common cells of origin during neurodevelopment. This process is controlled by a series of temporal transcription factors that are transiently expressed and drive the sequential production of specific progeny subtypes. Intermediate neural progenitors (INPs) and optic lobe neural stem cells (OL NSCs) share striking similarities in temporal factor expression despite divergent cells of origin. Tailless (Tll) is a terminal temporal factor in the visual system in OL NSCs. Its expression coincides with the termination of neurogenesis and onset of gliogenesis. Here, we report that Tll also acts as a terminal factor in Drosophila INPs, demonstrating functional conservation. Tll expression is activated by the preceding temporal factor Scarecrow, and represses odd-paired and hamlet. tll also plays a partial role in promoting gliogenesis in gliogenic NSCs. We performed genome-wide binding analysis of Tll in the OL NSCs and INPs by Targeted DamID, revealing both conserved and divergent targets, reflecting differences in regulatory outcomes. We show that temporal patterning mechanisms are conserved between different brain regions, whilst facilitating lineage-specific outputs.

Animals↗
PubMed1978

Neurogenesis in spinal cord of mouse: an autoradiographic analysis.

An autoradiographic analysis of the time and sites of origin, and the migration and settling patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10--14 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10 and 11 of gestation; the neurons in the intermediate gray region originated on days 11--14 of gestation; the neurons of the head of the dorsal horn originated on days 12--14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12--14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord.

Animals↗
PubMed2026

3D epigenome of glial cell types in developing human cortex.

The human cortex is complex and heterogeneous, undergoing extensive expansion during development1,2. Our prior study of neurogenesis, including radial glia (RG), intermediate progenitor cells, excitatory neurons and interneurons demonstrated that chromatin looping underlies transcriptional regulation for lineage-specific genes, shedding light on how non-coding genetic variants contribute to neuropsychiatric disorders by means of cell-type-specific gene regulation3. RG have a crucial role in generating cellular diversity through both neurogenesis and gliogenesis and can be further classified into ventricular RG (vRG) and outer RG (oRG)4,5. Given their significance in cortical development, we conducted a comprehensive three-dimensional (3D) epigenomic analysis of four main glial populations, including vRG, oRG, oligodendrocyte precursor cells and microglia, from the mid-gestational human neocortex. By integrating gene expression, chromatin accessibility, DNA methylation and 3D chromatin interactions, we identified cell-type-specific candidate cis-regulatory elements (cCREs) and validated their regulatory function using transgenic mouse embryos. Using machine learning, we prioritized 112 schizophrenia risk variants within glia cCREs and further confirmed the predicted vRG enhancer disruption by the rs4449074 risk allele in vivo. Finally, oRG cCREs are enriched for human accelerated regions compared with other cCREs and a subset of human accelerated regions show activity differences from their chimpanzee orthologues that interact with genes involved in neuronal development. Our findings advance the understanding of human-specific gene regulation during corticogenesis.

Journal Article↗
PubMed1979

[Similarities between cultured human fetal glia cells and cell types from gliomas; cell culture studies].

Authors carried out a comparative study of cell-cultures of human fetal brain tissue and gliomas of various histological structures. In 180-days long cultures of fetal brain tissue four types of cells could be distinguished: 1. large, polygonal cells, 2. small, round, immature glia-cells, 3. bipolar spongioblasts, 4. gliant astrocytes. These types of cells could not be identified with the cell types of adult human brain culture, but similar types of cells were found in cultures prepared of gliomas of different degree of malignancy. There is some evidence to suggest, that among these types of cells the most important are immature glial cells, since they seem to be multipotent and may play a part in the gliogenesis and in the formation of gliomas as well.

Astrocytoma↗
PubMed1978

Development of the indusium griseum. II. A semithin light microscopic and electron microscopic study.

Neurogenesis and gliogenesis in the indusium griseum were studied in semithin sections and with the electron microscope. Immature neurons were present at birth, but differentiated rapidly until, by 15 days, they appeared to be fully differentiated. At birth 38% of glia were glioblasts, 47% were immature astrocytes and 15% were mature microglia. Astrocyte differentiation appeared to occur earlier than in adjacent white matter. In the adult, 57% of glia were astrocytes, 21% were oligodendrocytes, and 22% were microglia. The volume density of neuronal nuclei did not change with age, but the volume density of neuronal perikaryon decreased from 34% at birth to 13% at 15 days, while the neuropil increased from 24% to 58%. Very few immature synapses were present at birth, but by 5 days a number of axodendritic synapses were present, and these increased with age.

Aging↗
PubMed1978

[Similarities between human fetal glia cells and glioma cell type in tissue cultures].

Comparative studies were carried out on cell cultures of human fetal brain tissue and of gliomas of different tissue structures. In the cultures of fetal brain tissue maintained for 180 days, four cell-types could be distinguished: 1 large polygonal cells showing epithelial type growth; 2 groups of small round cells; 3 bipolar spongioblasts; and 4 giant astrocytes. The monolayers consisting of large cells formed a nursing layer for the small round cells and could be considered neuroepithelial cells. The small round cells forming groups were regarded as immature gliacytes which created migrational forms by means of active motion. The bipolar spongioblasts were considered a variant of the immature gliacytes. The giant astrocytes displayed the lowest plasticity; their appearance was interpreted as a true differentation and not simply as a change in form of one of the cell types. The cells of the fetal brain tissue could not be identified with the cells of the adult human brain. Still, all the four cell types appeared in the cultures of gliomas with different textures and different degrees of malignity. It seems that with respect to gliogenesis, among the four described cell types the immature gliacytes are of the greatest importance.

Astrocytoma↗