Disruption of polyamine modulation by a single amino acid substitution on the L3 loop of the OmpC porin channel

The development of Antechinus stuartii from the 2-cell stage to the blastocyst stage in vivo was examined by routine transmission electron microscopy. The 2-8-cell stages had a similar organization of organelles, whereas the 16- to 32-cell stages had pluriblast cells and trophoblast cells forming an epithelium closely apposed to the zona pellucida. Specialized cell-zona plugs were formed at the 8-cell stage, and primitive cell junctions appeared in later conceptuses. The cytoplasmic organelles included mitochondria, lysosomes, aggregates of smooth endoplasmic reticulum, lipid and protein yolk bodies and fibrillar arrays, possibly contractile in function. Nuclei had uniformly-dispersed dense chromatin. Nucleoli of 2-4-cell conceptuses were dense, compact and fibrillar, and those of 8-cell conceptuses and later conceptuses were finely granular and became progressively reticulated. The embryonic genome is probably not switched on before the 8-cell stage. Sperm tails were detected in cells in several early conceptuses. The yolk mass had the same organelles as cells. Centrioles were discovered for the first time in marsupial conceptuses. These were prominently situated at a spindle pole in a 32-cell blastomere and were associated with a nucleus and sperm tail at the 4-cell stage. It is very likely that the paternal centrosome is inherited at fertilization and perpetuated in Antechinus embryos during cleavage.     

Progressive cortical synchronization of ponto-geniculo-occipital potentials during rapid eye movement sleep

Phasic events, termed ponto-geniculo-occipital potentials, appear in the brainstem, thalamus and cerebral cortex during rapid eye movement sleep. In the cat, the species of choice for ponto-geniculo-occipital studies, these field potentials are usually recorded from the lateral geniculate thalamic nucleus and visual cortex. However, the fact that brainstem cholinergic neurons play a crucial role in the transfer of ponto-geniculo-occipital potentials to the thalamus, coupled with the evidence that mesopontine tegmental neurons project to virtually all thalamic nuclei, together explain why ponto-geniculo-occipital potentials are recorded over widespread territories, beyond the visual thalamocortical system. Here we demonstrate, by means of multi-site unit and field potential recordings from sensory, motor and association cortical areas in behaving cats, that: (i) ponto-geniculo-occipital potentials appear synchronously over the neocortex; and (ii) that their cortical synchronization develops progressively from the period preceding rapid eye movement sleep by 30-90 s (pre-rapid eye movement), to reach the highest degree of intracortical coherence during later epochs of rapid eye movement sleep. We propose that the widespread coherence of cortical ponto-geniculo-occipital potentials underlies the synchronization of fast oscillations (30-40 Hz) during rapid eye movement sleep over many, functionally distinct cortical territories implicated in dreaming, as brainstem-induced ponto-geniculo-occipital-like potentials are consistently followed by such fast oscillations.     

Restrictive clonal allocation in the chimeric mouse brain

Whether, and to what extent, lineage restriction contributes to the organization of the mammalian brain remains unclear. Here we address this issue by examining the distribution of clonally related cells in chimeric mice generated by injecting genetically tagged embryonic stem (ES) cells into blastocyst embryos. Our examination of postnatal chimeric brains revealed that the vast majority of labeled ES cell descendents were confined within a different subset of brain regions in each animal. Moreover, the deployment of labeled cells in different brain regions was distinctive. The pattern of ordered and binomial colonization suggested that early diversified founder cells may constrain the fates of their descendants through a restriction of dispersion. In addition, the symmetrical distribution of ES cell descendants suggests that bilaterally corresponding structures may arise from a common set of progenitor cells. Finally, clones of cells formed a continuous band within the deep strata of the neocortex. This later finding in conjunction with the radial distribution of clones in remaining layers observed in previous studies indicates that the cerebral neocortex may derive from two groups of founder cells, which is consistent with the hypothesis of dual phylogenetic origins of the mammalian cerebral cortex.     

Development of commissural neurons in the wallaby (Macropus eugenii)

We have examined the development of the laminar and areal distribution of cortical commissural neurons in a marsupial mammal, the wallaby Macropus eugenii. In this species, commissural axons approach the major cerebral commissure, the anterior commissure, via either the internal capsule or the external capsule and first cross the midline at postnatal day 14 (P14). By retrogradely labelling these axons with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI) at P15, we show here that the cell bodies of these neurons are restricted to a region of cortex adjacent to the rhinal fissure. Most of these labelled neurons are located in the compact cell zone of the cortical plate, with only a few labelled cells found in the zone of loosely packed cells deep to this layer. Over the subsequent 66 days, commissural neurons are found progressively more dorsally, rostrally, and caudally, so that, by P80, they are present throughout the extent of the neocortex. At this age, they are mainly pyramidal in morphology and form a single band within the deeper part of layer 5 of the developing cortex. From P80 to adulthood, the distribution of commissural neurons has been assessed in the visual cortex by using retrograde transport of horseradish peroxidase. At P80, labelled neurons with immature pyramidal morphology are present throughout the occipital cortex; as in DiI material, somata are located in deep layer 5. At P165, previously shown to be the age when commissural axon numbers peak, widespread labelling is present in the occipital region, with labelled cells now found in two bands corresponding to layers 3 and 5. After this age, neurons become more restricted in distribution, so that, by adulthood, commissural neurons are no longer apparent throughout area 17 but are restricted to a localised region around the area 17/18 boundary. Within this region, labelling is still present in layers 3 and 5 but is more dense in layer 3. The gradual restriction of commissural fields seen here in the wallaby is similar to that reported in the neocortex in many eutherians. These findings also support studies in eutheria, suggesting that subplate neurons do not appear to play a major role in commissural development.     

Dendritic translocation of RC3/neurogranin mRNA in normal aging, Alzheimer disease and fronto-temporal dementia

RC3/neurogranin is a postsynaptic protein kinase C (PKC)-/calmodulin-binding substrate implicated in long-term potentiation (LTP) forms of synaptic plasticity. Our previous digoxigenin in situ hybridization (DIG-ISH) studies detected RC3 mRNA in apical dendrites and cell bodies of neurons in the rat cerebral cortex and hippocampus. This observation suggested that RC3 mRNA is selectively translocated to dendrites, where it may be translated locally in response to synaptic activity. To test this hypothesis further, we isolated a full-length cDNA clone of the homologous human RC3 mRNA from a human cortex lambda GT11 library, determined its nucleotide and predicted amino acid sequences, and performed mRNA expression studies in cerebral cortex from normal human patients and from patients with Alzheimer disease (AD) and fronto-temporal dementia (FTD). The human cDNA clone detects a single approximately 1.3 kb mRNA whose nucleotide sequence is 73% similar to the rat nucleotide sequence and 96% similar to its amino acid sequence. DIG-ISH studies detect robust staining of RC3 mRNA in cell bodies of numerous neurons throughout Layers II-VI and in both apical and basal dendrites of pyramidal neurons in human neocortex (temporal/frontal). We conclude that dendritic targeting of RC3 mRNA is conserved in human brain. In AD neocortex tissue, there is little or no evidence for RC3 mRNA translocation to dendrites, while in FTD neocortex, targeting of RC3 mRNA to apical dendrites is preserved. Comparative studies in AD and FTD point to the potential importance of synapse integrity and the dendritic cytoskeleton in RC3 mRNA targeting in the human neocortex.     

Variability and partial synchrony of the cell cycle in the germinal zone of the early embryonic cerebral cortex

Cell cycle parameters were estimated using the cumulative 3H-thymidine S-phase labeling and percentage of labeled mitoses methods in the embryonic day 14 and 15 germinal zone of the rat cerebral cortex. The shortest cell cycle time was seen in the dorsal neocortex and the longest in the lateral neocortex and fimbria (the latter also had a low growth fraction). No differences were observed in cell cycle times between the cells in the ventricular and subventricular zone in the same neocortical region. The results suggest gradients of lengthening cell cycle times extending ventrolaterally and ventromedially from the dorsomedial neocortex. Although a majority of proliferating cells in individual cortical regions seem to belong to one population in terms of cell kinetics, several pieces of evidence suggest some heterogeneity: the asymmetric shapes of the percentages of labeled mitoses curves, the small population of noncycling neuroepithelial cells in the neocortex and mesocortex, and small population of cells that become pyknotic. Groups of DNA-synthesizing nuclei that were ectopically located in the inner half of the ventricular zone also indicate the existence of different subpopulations of neuroepithelial cells. In addition, after a pulse injection of 3H-thymidine the germinal zone is characterized by alternating clusters of heavily and lightly labeled cell nuclei that may reflect the simultaneous passage of a cluster of cells through the same portion of S-phase. We suggest that partial cell cycle synchrony within groups of ventricular cells may explain the presence of these iterative cell kinetic patterns in the developing cortex.     

Control of Swe1p degradation by the morphogenesis checkpoint

In the budding yeast Saccharomyces cerevisiae, a cell cycle checkpoint coordinates mitosis with bud formation. Perturbations that transiently depolarize the actin cytoskeleton cause delays in bud formation, and a 'morphogenesis checkpoint' detects the actin perturbation and imposes a G2 delay through inhibition of the cyclin-dependent kinase, Cdc28p. The tyrosine kinase Swe1p, homologous to wee1 in fission yeast, is required for the checkpoint-mediated G2 delay. In this report, we show that Swe1p stability is regulated both during the normal cell cycle and in response to the checkpoint. Swe1p is stable during G1 and accumulates to a peak at the end of S phase or in early G2, when it becomes unstable and is degraded rapidly. Destabilization of Swe1p in G2 and M phase depends on the activity of Cdc28p in complexes with B-type cyclins. Several different perturbations of actin organization all prevent Swe1p degradation, leading to the persistence or further accumulation of Swe1p, and cell cycle delay in G2.     

Cerebral cortical specification by early potential restriction of progenitor cells and later phenotype control of postmitotic neurons

Neurons expressing latexin, a carboxypeptidase A inhibitor, are restricted to lateral areas in the cerebral cortex of adult and early postnatal rats. To address the precise timing of cortical regional specification at the cellular level, we monitored latexin expression in developing cortical cells under specific conditions in vitro. Individual cortical cells were labeled with 5-bromo-2'-deoxyuridine in vivo, dissociated and exposed to a defined new environment in a monolayer or a reaggregated-cell culture system. While a substantial fraction of early progenitor cells derived from the lateral cerebral wall became latexin-expressing neurons in both systems, far fewer progenitors from dorsal cortex did so under the same environmental conditions, indicating early establishment of cortical regional specification at the progenitor cell level. Furthermore, it was shown that the probability for postmitotic cells within lateral cortex to become latexin-expressing neurons was influenced by temporally regulated regional environmental signals. These findings suggest that developing cortical cells are progressively specified for a regional molecular phenotype during both their proliferative and postmitotic periods.     

Spontaneous excitatory postsynaptic currents in hippocampal CA1 pyramidal neurons of the gerbil after transient ischemia

The changes in the spontaneous excitatory postsynaptic currents (sEPSCs) after transient cerebral ischemia were studied using whole-cell recording from CA1 pyramidal neurons in the gerbil. In neurons recorded 1-2 days after ischemia, sEPSCs had a slowed time course with the decay time constant fitted by a single exponential and it progressively increased after ischemia. Frequency and amplitude distribution of sEPSCs in ischemic neurons were not significantly different from those in the control neurons. The results support the view that abnormal non-N-methyl-D-aspartic acid currents originate at the degenerated postsynaptic site, unrelated to the presynaptic releasing mechanisms.     

Purification of recombinant apolipoprotein A-1Milano expressed in Escherichia coli using aqueous two-phase extraction followed by temperature-induced phase separation

Immunohistochemistry using anti-human neuron-specific enolase (NSE) mouse monoclonal antibody was performed in human brains from autopsy cases, which enabled us to assess the neuronal damage besides hematoxylin and eosin or Klüver-Barrera stain. Neurons in cerebral neocortex which showed necrotic changes such as prominent cytoplasmic vacuolization or cellular shrinkage with nuclear pyknosis showed a tendency to be less stained by anti-NSE antibody. Anti-NSE immunostaining was statistically significantly less in the neocortex from CO intoxication than from other causes of death, although morphological necrotic changes were less observed in CO intoxication. Hippocampal CA1 neurons clearly lost NSE immunoreactivity with the progression of necrotic changes. Neurons in CA2 were statistically significantly better stained by anti-NSE antibody than in CA1, 3, and 4. Cerebellar Purkinje cells were poorly stained by anti-NSE antibody, whereas neurons in cerebellar dentate nucleus and inferior olive in medulla oblongata were better stained. Anti-NSE immunostaining was lost in the injured areas of the cerebral neocortex while neurons in the intact areas were better stained in brain injury. These results indicate that anti-NSE immunostaining of neurons could reflect vital reaction and could be useful in evaluating neuronal damage in the hippocampal CA1 region or brain injury.     

Alterations in the cell cycle of mouse cumulus granulosa cells during expansion and mucification in vivo and in vitro

The cell cycle characteristics of mouse cumulus granulosa cells were determined before, during and following their expansion and mucification in vivo and in vitro. Cumulus-oocyte complexes (COC) were recovered from ovarian follicles or oviducts of prepubertal mice previously injected with pregnant mare serum gonadotrophin (PMSG) or a mixture of PMSG and human chorionic gonadotrophin (PMSG+hCG) to synchronize follicle differentiation and ovulation. Cell cycle parameters were determined by monitoring DNA content of cumulus cell nuclei, collected under rigorously controlled conditions, by flow cytometry. The proportion of cumulus cells in three cell cycle-related populations (G0/G1; S; G2/M) was calculated before and after exposure to various experimental conditions in vivo or in vitro. About 30% of cumulus cells recovered from undifferentiated (compact) COC isolated 43-45 h after PMSG injections were in S phase and 63% were in G0/G1 (2C DNA content). Less than 10% of the cells were in the G2/M population. Cell cycle profiles of cumulus cells recovered from mucified COC (oviducal) after PMSG+hCG-induced ovulation varied markedly from those collected before hCG injection and were characterized by the relative absence of S-phase cells and an increased proportion of cells in G0/G1. Cell cycle profiles of cumulus cells collected from mucified COC recovered from mouse ovarian follicles before ovulation (9-10 h after hCG) were also characterized by loss of S-phase cells and an increased G0/G1 population. Results suggest that changes in cell cycle parameters in vivo are primarily mediated in response to physiological changes that occur in the intrafollicular environment initiated by the ovulatory stimulus. A similar lack of S-phase cells was observed in mucified cumulus cells collected 24 h after exposure in vitro of compact COC to dibutyryl cyclic adenosine monophosphate (DBcAMP), follicle-stimulating hormone or epidermal growth factor (EGF). Additionally, the proportion of cumulus cells in G2/M was enhanced in COC exposed to DBcAMP, suggesting that cell division was inhibited under these conditions. Thus, both the G1-->S-phase and G2-->M-phase transitions in the cell cycle appear to be amenable to physiological regulation. Time course studies revealed dose-dependent changes in morphology occurred within 6 h of exposure in vitro of COC to EGF or DBcAMP. Results suggest that the disappearance of the S-phase population is a consequence of a decline in the number of cells beginning DNA synthesis and exit of cells from the S phase following completion of DNA synthesis. Furthermore, loss of proliferative activity in cumulus cells appears to be closely associated with COC expansion and mucification, whether induced under physiological conditions in vivo or in response to a range of hormonal stimuli in vitro. The observations indicate that several signal-transducing pathways mediate changes in cell cycle parameters during cumulus cell differentiation.     

Changes in the distribution of intermediate filaments in rat Sertoli cells during the seminiferous epithelium cycle and postnatal development

BACKGROUND: Intermediate filaments (IFs) are components of the cytoskeleton. In mammalian Sertoli cell, IFs are formed by vimentin. Previous studies have shown some characteristics of its distribution in Sertoli cells, however, very little is known of its distributional changes during the seminiferous epithelium cycle and during postnatal development. METHODS: Immunohistochemical and electron microscopic methods were used to determine the distribution of vimentin-type IFs in rat Sertoli cells during the seminiferous epithelium cycle and postnatal development. RESULTS: The distribution of IFs in adult rat Sertoli cell showed distinct cyclic changes during the seminiferous epithelium cycle. At stages I-VI, bundles of IFs extend from the perinuclear region to the supranuclear and apical regions of the Sertoli cell. These apical extensions became shorter at stage VII, and at stages VIII-X IFs were observed only in the perinuclear region. Short apical extensions reappeared at stages XI-XII; and at stages XIII-XIV, they extended again into the apical region. During this cycle, IFs were always closely associated with the heads of elongate spermatids. IFs were also shown to be in close apposition to some specialized structures on the cell membrane, such as the ectoplasmic specialization between adjacent Sertoli cells. During postnatal (p.n.) development, IFs were mainly observed at the basal nuclear region on p.n. day 7. The IFs in the supranuclear or apical regions first appeared at p.n. day 14 and gradually increased during the development. The perinuclear IFs network was fully established by p.n. day 28 and the adult distribution pattern of the IFs was established by p.n. day 42. CONCLUSIONS: Vimentin-type IFs in rat Sertoli cells are a delicate endocellular network, which is centered in the perinuclear region and extends to the apical region of the cell. During the seminiferous epithelium cycle, the distribution of IFs changes in a stage-dependent manner and is closely related to the location of the heads of elongate spermatids. During postnatal development, IFs gradually increase in numbers and the main distribution area is transferred from the basal nuclear to the perinuclear and supranuclear regions.     

Transarterial embolization of the uterine arteries: patient reactions and effects on uterine vasculature

Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.     

Cyclin A, cyclin B and stringlike are regulated separately in cell cycle arrested trochoblasts of Patella vulgata embryos

Trochoblasts are the first cells to differentiate during the development of spiralian embryos. Differentiation is accompanied by a cell division arrest. In embryos of the limpet Patella vulgata, the participation of cell cycle-regulating factors in trochoblast arrest was analysed as a first step to unravel its cause. We determined the cell cycle phase in which the trochoblasts are arrested by analysing the subcellular locations of mitotic cyclins. The results show that the trochoblasts are most likely arrested in the G2 phase. This was supported by measurement of the DNA content in trochoblast nuclei after the last division. Trochoblasts complete their final division at the sixth mitotic cycle. This mitotic cycle resembles the first postblastoderm cell cycle of Drosophila, in which mitotic activity is controlled by expression of the string gene. As failure of string expression results in cell cycle arrest in the G2 phase, negative regulation of a Patella string homolog could be responsible for trochoblast arrest. Although Stl messengers disappeared from trochoblasts during their final division, expression was observed again 20 min later. Messengers remained present in all trochoblasts at low levels during further development. Thus, expression of the stringlike gene allows the cell cycle arrest of these cells, whereas in Drosophila cells arrested in division lack string messengers.     

Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor

Reactive oxygen species generated during the metabolism of the antitumor quinone 3,6-diaziridinyl-1,4-benzoquinone (DZQ) in human colonic carcinoma HCT116 cells lead to the induction of p21 (WAF1, Cip1, or sdi1), an upstream regulator of the retinoblastoma gene product pRb involved G1 cell cycle control. We here demonstrate that the cell cycle was arrested in G2/M phase following supplementation with DZQ of human osteosarcoma Saos-2 cells (lacking both p53 and pRb) and HCT116 cells. DZQ also induced p21 and apoptosis in Saos-2 cells. The transfection of the Rb gene into Saos-2 cells did not alter the level of p21 induction, but changed cell cycle arrest into G1 phase and prevented apoptosis. These findings suggest that quinones may lead to a p53-independent and pRb-preventable G2/M arrest and apoptosis, which correlate with p21 induction.     

Distribution of nitric oxide synthase in the esophagus of the cat and monkey

The distribution of nitrergic neurons and processes in the esophagus of the cat and monkey was studied by light microscopic immunocytochemistry using a specific antibody against purified rat brain nitric oxide synthase and immunoperoxidase procedures. Immunoreactive nerve fibers were found pervading the myenteric plexus, submucous plexus and plexus of the muscularis mucosae, and particularly in the lower esophagus a few immunoreactive fibers entered the epithelium as free nerve endings, some of which derived from perivascular fibers. In the upper esophagus immunoreactive motor end-plates were found in the striated muscle. Thirty-forty-five percent of neuronal cell bodies found in the intramural ganglia and along the course of nerve fiber bundles were immunoreactive and were of the three morphological types earlier described. In the intramural ganglia immunoreactive nerve fibers formed a plexus in which varicose nerve terminals were in close relation to immunoreactive and non-immunoreactive neurons. The intramural blood vessels that crossed the different layers of the esophageal wall were surrounded by paravascular and perivascular plexuses containing immunoreactive nerve fibers. The anatomical findings suggest that nitric oxide is involved in neural communication and in the control of peristalsis and vascular tone in the esophagus. In the lower esophagus a few nitrergic nerve fibers are anatomically disposed to subserve a sensory-motor function.     

Immunolocalization of inhibin and activin subunits in human endometrium across the menstrual cycle

Inhibin/activin alphaC/alphaN and betaA subunits were localized immunohistochemically in the human endometrium throughout the menstrual cycle using an affinity-purified sheep polyclonal antibody raised against the alphaC/alphaN subunit and an affinity-purified rabbit polyclonal antibody raised against the betaA subunit. The betaB subunit was below the level of detection in all human endometrial samples tested. Immunoreactive inhibin alphaC/alphaN subunit was localized in the luminal epithelium, glandular epithelium, stromal tissues and vascular endothelium with no significant variation across the normal menstrual cycle. Immunoreactive betaA subunit, common to inhibin A and activins AA and AB was localized in the luminal and glandular epithelium and in migratory cells while the endometrial stromal cells, decidua, vascular smooth muscle and endothelium were devoid of immunoreactivity. A significant variation of immunoreactive betaA subunit was observed in glandular and luminal epithelium across the normal menstrual cycle. In proliferative endometrium, only a very low level of betaA immunostaining was seen in luminal and glandular epithelium, while the luminal epithelial staining increased significantly in the early secretory phase and remained relatively constant over the rest of the menstrual cycle. A progressive increase in betaA immunoreactivity was observed also in the glandular epithelium during the secretory phase reaching a maximum in the late secretory phases, and decreasing at menstruation. Co-localization studies on serial sections suggested that the migratory cells expressing strong betaA immunoreactivity were macrophages and neutrophils but not eosinophils or mast cells. Thus, cells within the human endometrium are capable of expressing inhibin/activin molecules in vivo. The variation in the pattern of secretion of the betaA subunit across the menstrual cycle suggests that activin peptides may have a physiological role in endometrial function.     

Patterns of DNA synthesis and mitotic activity during the intermoult of Daphnia

Among insects, the epidermal cell cycle pattern is related to the type of ontogenetic development. In taxa undergoing complete metamorphosis, cells are commonly maintained in the G2 stage of interphase between bouts of cell division. In crustaceans, as in insects exhibiting incomplete metamorphosis, it is believed that cells ordinarily remain in G1 for much of the intermoult, with DNA replication occurring late in the moult cycle followed closely by cell division. The present study reveals a differing pattern of epidermal cell division in two distantly related members of the cladoceran crustacean genus Daphnia. Cell cycle kinetics were examined in the last juvenile instar of each species using DNA content determinations and estimates of mitotic frequency. These analyses confirm that each epidermal cell possessed the diploid DNA amount, completed a single cell cycle, and remained in G1 for the majority of the instar. However, DNA replication occurred shortly after moulting and was followed by intense mitotic activity so that cell proliferation was restricted to a short period soon after ecdysis. Cell densities during the instar increased by approximately 60 and 100% for D. pulex and D. magna, respectively.     

Early events in the histo- and cytogenesis of the vertebrate CNS

Development of the vertebrate, viewed on the cellular level, proceeds by sequential steps in which potencies of progenitor cells become progressively and irreversibly restricted. This is known as progression of the major differentiation. Cytogenesis of the CNS may be regarded as one typical example. The period of cytogenesis in the CNS is divided into three consecutive stages. In stage I, the wall of the neural tube is composed solely of matrix cells. In stage II, i.e., the stage of neuronogenesis, some of the daughter matrix cells are determined at the early G1 phase to be differentiated into neuroblasts. The specificity of individual neurons appears to be irreversibly determined at the time of birth of the neuroblasts, as a function of time-and-place of their production. The individual matrix cells that have existed at the very beginning of neurogenesis give birth to a series of progressively different types of neurons in stage II as the major differentiation proceeds. Finally, matrix cells cease to produce neurons. This is the end of stage II. Thereafter, only non-neuronal cells, namely neuroglia and ependymal cells, are produced. This is stage III or the stage of neuroglia production. The sequential nature of the differentiative behavior of matrix cells can be explained by the hypothesis of progressive gene inactivations that accumulate in genomes of matrix cells during development. Different types of neurons are produced from matrix cells at different states of the "major differentiation".(ABSTRACT TRUNCATED AT 250 WORDS)