Histogenetic Cell Death Research Articles

Особенности реализации основных закономерностей гистогенеза тканей шейки матки крыс в ходе постнатального онтогенеза

Electron microscopic examination of the postnatal development of the tissues of the rats’ uterine cervix at the level of the sphincter was performed. It has been established that at the time of rats' birth the processes of histogenesis are not complete. Cervical sphincter becomes definitive structure only at the time of puberty. After birth and until the onset of puberty, the processes of cell proliferation, genetically programmed cell death, differentiation and integration continue in the uterine cervix. Intensity of these processes at different stages of postnatal development varies. The process of proliferation of cells, which is expressed maximally after birth of the animals, promotes the formation of layers of the uterine cervix and the walls of the myometrium. At the same time with active proliferation, signs of a specific differentiation and integration of tissues into a complex apparatus - cervical sphincter occurs. Histogenetic cell death in the cervical wall is observed throughout postnatal period, but it has a maximum value at the first month of life and in aging animals. In the first case, apoptosis plays a leading role in the formative processes; in the second case, it indicates a decrease in the functional activity of specialized tissues.

La mort, un élément essentiel de la vie intra-utérine

The development and formation of an organ needs both cell proliferation and cell death. It is commonly possible to decipher three types of basic cell death: 1) the so-called morphogenetic cell death (an example is the formation of the digits); 2) the histogenetic cell death like the apoptotic processes taking place in the spinal cord and allowing to regulate the number of motoneurons according to their targets; and 3) the phylogenetic cell death in which vestigial structures are selectively removed (e.g. destruction of the pronephros or removal of the tail in the anuran larva).

Prenatal and Postnatal Contents of Amino Acid Neurotransmitters in Mouse Parietal Cortex

This study documents the variation in the amino acid neurotransmitter contents during mouse parietal cortex development, from embryonic day 13 (E13) until young adulthood, between postnatal day 21 (P21) and P30. Taurine, an inhibitory neurotransmitter and neuromodulator, is the most abundant neurotransmitter in the developing neocortex, whereas, at the adult stage, glutamate is the more prominent neurotransmitter playing an excitatory role, and GABA is the major inhibitory neurotransmitter. During the proliferative stage of neurogenesis in the mouse cerebral cortex, between E13 and E17, relatively high levels of glutamate, aspartate, taurine and glycine were detected, consistent with a possible trophic influence of these neurotransmitters during cortical development prior to synaptogenesis. Between E17 and E19, a significant decline in the contents of these neurotransmitters was observed, consistent with earlier reports of cell death in the ventricular and subventricular zones during this stage of development. During the perinatal period, a progressive increment in glutamate level was seen between E21 and P5, and then the values remained constant until the second postnatal week. Glutamate also decreased by about 25% between P11 and P15, on the other hand, aspartate diminished by about 20% between P7 and P9. These results were consistent with previous reports of histogenetic cell death during the first 2 postnatal weeks in mouse neocortex. GABA increased from the embryonic period until young adulthood, in contrast, the glycine content decreased; thus, in the adult parietal cortex, the GABA content was about 2.6-fold higher than that of glycine. During the first postnatal week, the concentrations of glutamate and GABA showed significant increments between P0 and P5, while those of aspartate and glycine remained constant. During this period, amino acids are predominantly excitatory and the cerebral cortex is vulnerable to epileptiform activity; the significant increment in taurine content between P0 and P3 suggests a neuroprotective action of taurine against excitotoxicity. At P15, coinciding with the period of maximum cortical synaptogenesis, significant increments in GABA and glycine contents were observed which could be related to the maturation of inhibitory synaptic transmission. At the young adult stage, there was a rise in the levels of both excitatory neurotransmitters, glutamate and aspartate, and a significant reduction in the contents of all three inhibitory neurotransmitters, GABA, glycine and taurine.

Programmed cell death in the developing heart.

In humans every minute millions of cells die by programmed cell death and by the end of their life almost 99.9% of all cells once made have undergone this fate [1]. The functionality of cell death is different during development and adult life. During development apoptosis serves three major functions: deleting vestigial structures, i.e. phylogenetic cell death; controlling cell numbers, i.e. histogenetic cell death, and remodeling structures, i.e. morphogenetic cell death [2]. In adult life, apoptosis mainly serves to maintain homeostasis by counterbalancing mitosis and deleting cells, which are potentially autoimmunoreactive, malignant, or virus infected [3,4]. In contrast to adult life cell death, where cell death is generally considered a pathological event, during cardiac development cell death is a physiological event that is highly regulated in space and time. It took till 1968 when cell death was first recognized in the chicken ventricular myocardium [5]. In the next decade, the spatiotemporal pattern of cell death in the developing heart was extensively studied, in particular by the groups of Pexieder [6–10], Okamoto [11–14] and Ojeda [15–18]. These studies accurately described cell death patterns, but the underlying mechanisms and functions were not addressed. Despite the large body of data regarding the spatiotemporal patterns of cell death in the developing heart, a comprehensive overview of cell death in this developing organ is difficult to obtain. This is mainly because the original data were not published in regular journals and/or in the German language. Moreover, the nomenclature of the various structures of the developing heart has changed significantly during the last decades, which adds to the imperviousness of the data. The objective of this review is to bring together data derived from the earlier as well as from recent studies, and to generate a map of cardiac cell … * Corresponding author. Tel.: +31-20-5669-111; fax: +31-20-6976-177 m.j.vandenhoff{at}amc.uva.nl a.f.moorman{at}amc.uva.nl

Sequence of Neuron Origin and Neocortical Laminar Fate: Relation to Cell Cycle of Origin in the Developing Murine Cerebral Wall

Neurons destined for each region of the neocortex are known to arise approximately in an "inside-to-outside" sequence from a pseudostratified ventricular epithelium (PVE). This sequence is initiated rostrolaterally and propagates caudomedially. Moreover, independently of location in the PVE, the neuronogenetic sequence in mouse is divisible into 11 cell cycles that occur over a 6 d period. Here we use a novel "birth hour" method that identifies small cohorts of neurons born during a single 2 hr period, i.e., 10-20% of a single cell cycle, which corresponds to approximately 1.5% of the 6 d neuronogenetic period. This method shows that neurons arising with the same cycle of the 11 cycle sequence in mouse have common laminar fates even if they arise from widely separated positions on the PVE (neurons of fields 1 and 40) and therefore arise at different embryonic times. Even at this high level of temporal resolution, simultaneously arising cells occupy more than one cortical layer, and there is substantial overlap in the distributions of cells arising with successive cycles. We demonstrate additionally that the laminar representation of cells arising with a given cycle is little if at all modified over the early postnatal interval of histogenetic cell death. We infer from these findings that cell cycle is a neuronogenetic counting mechanism and that this counting mechanism is integral to subsequent processes that determine cortical laminar fate.

Apoptosis: Final common pathway of photoreceptor death in rd, rds, and mutant mice

Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice. Although the phenotypes arising from these mutations are different, suggesting different mechanisms of pathogenesis, we present evidence that apoptosis may be the final common pathway of the disease process linking genotype to phenotype. We observed internucleosomal cleavage of retinal DNA by gel electrophoresis and fragmented DNA at the single cell level by labeling the nicked DNA ends with biotinylated poly(dU). In retinal degeneration mice, DNA fragmentation occurred during the period of photoreceptor degeneration. In retinal degeneration slow mice and in transgenic mice expressing a mutant (Pro347Ser) rhodopsin gene, DNA fragmentation occurred after normal histogenetic cell death (also apoptosis) had ceased. Since DNA fragmentation by internucleosomal cleavage is a cardinal feature of apoptosis, our data suggest that all three of these genetic mutations lead to apoptosis.

Rat retinal ganglion cells express Ca 2+-permeable non-NMDA glutamate receptors during the period of histogenetic cell death

Local application of glutamate agonists to retinal ganglion cells (RGNs) was performed in retinae isolated from pigmented rats aged between 3 and 8 days postnatally. A vast majority of RGNs displayed current responses to glutamate (Glu), N-methyl- d-aspartate (NMDA), quisqualate (QA), α-amino-2,3-dihydro-5-methyl-3-oxo-4-isoazolepropanoic acid (AMPA), kainate (KA) and domoate (DA). In Na +-free extracellular solution with elevated Ca 2+, non-NMDA agonists elicited large (up to 200 pA) inward currents that were completely blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX) and Cd 2+. MK-801 also induced a partial block of cationic currents in Na +-free saline. In standard salt solutions, current-voltage relationships of Glu-R-mediated currents were often inwardly rectifying in the presence of d-aminophosphonovalerat (D-APV), as is typical of Ca 2+-permeable non-NMDA receptors. The presence of inward rectification in the current voltage relationship was always associated with a high value of the cationic permeability ratioP Ca 2+/ P Cs + (>0.8). However, in about half of the investigated RGNs no inward rectification was observed under standard recording conditions. Our results lead to the suggestion that expression of Ca 2+-permeable Glu receptor subunits may contribute to regulation of cell numbers in the postnatal retina.

A quantitative model for the regulation of naturally occurring cell death in the developing vertebrate nervous system

Throughout the animal kingdom, the formation of the nervous system involves the elimination of many cells soon after their generation. This phenomenon, known as naturally occurring cell death, has precise time schedules and is observed in the vast majority of neural structures. It causes the loss of 15-85% of the neurons generated. Manipulations of the target structure can considerably affect the amount of cell death in a nervous center, but the regulation of this process is still controversial. While in some experiments cell death leads to a linear relationship between the size of the target and that of the input, other experiments show dramatic deviations from a linear prediction. It is quite possible that cell death is regulated by different mechanisms in different cases and that the search for a single explanation would be doomed to failure. However, it is shown here that if mutual trophic interactions are assumed to occur between connected structures, a general model can be developed for the regulation of histogenetic cell death in the developing nervous system of vertebrates. The model relies on few assumptions, all derived from a number of experimental studies. Cells destined to form a neural center are generated according to a program and die around a certain age unless a trophic factor is supplied that prevents their death. Target cells exert a trophic influence on input cells and vice versa. The model quantitatively describes the time course and the amount of cell death in neural structures, thereby reconciling in a unitary framework experimental findings that until now have appeared conflicting.

Effect of thyroid deficiency on the development of glia in the hippocampal formation of the rat: an immunocytochemical study.

The development of glia in the hippocampal formation of normal and hypothyroid rats was studied using immunocytochemical staining for either glial fibrillary acidic protein (GFAP) or vimentin. Light microscopy showed lower GFAP immunoreactivity in the radial glial processes of young hypothyroid rats compared to normal animals. These processes followed the known path of neuroblast migration toward the proliferative zone of the dentate gyrus until the end of the 1st postnatal week. Vimentin immunoreactivity showed that the glial processes were present and therefore immature at least with respect to their cytoskeletal composition. We propose that this early defect in the maturation of the radial glial fibers accounts for the final deficit in the granule cells of the dentate gyrus. Later in development, thyroid deficiency also reduced the density and number of GFAP-labeled astrocytes and the growth of their processes. This observation is in complete disagreement with the glial hypertrophy induced by thyroid deficiency in the cerebellum. The considerably increased histogenetic cell death observed in the cerebellum of young hypothyroid rats could in turn induce glial hypertrophy, whereas the hippocampal formation, where a normal low number of cell deaths is observed, is only subjected to the general depressive effect of thyroid deficiency on cell maturation.

Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras

Cell death is a common yet puzzling feature of the development of many populations of neurons in the CNS. In the invertebrate phyla, such death is often preprogrammed; by contrast, in vertebrates, the best studied examples of histogenetic cell death are influenced by interactions among the neurons and their target. One attempt to explain this seemingly wasteful scheme of development has led to the hypothesis that this target-related cell death allows 2 populations of cells, which develop in isolation, to come into numerical and functional balance and hence to provide an epigenetic "buffer" mechanism to accommodate developmental variations. In the current study we have examined the extent to which the cell death observed in the cerebellar granule cell population serves to numerically match these neurons with their primary postsynaptic target, the Purkinje cell. Staggerer chimeras were made by aggregating 8-cell staggerer embryos with embryos of wild-type genotype. The cerebella of the resulting animals developed with widely varying numbers of normal (wild-type) Purkinje cell targets. Although staggerer Purkinje cells were present in the chimeric brains, these cells are intrinsically deficient in their normal developmental program (in the mutant, because of this deficiency, 100% of the granule cells die). Both granule cells and Purkinje cells were counted in chimeras and several wild-type mice. The results reveal that the number of granule cells present in these brains has a linear relationship with the number of Purkinje cells, and that the line connecting the points intersects the Y-axis close to the origin. These observations suggest that numerical matching is an important function of target-related cell death in the granule cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of the mechanisms underlying increased histogenetic cell death in developing cerebellum of the hypothyroid rat: determination of the time required for granule cell death

The connection between the date of formation of granule cells and their final position in the internal granular layer of the cerebellum has been described previously. In rats made hypothyroid since the end of gestation, the distribution of the pyknotic cells in the internal granular layer of the cerebullar cortex was also previously found to be age-related. In 14-day-old hypothyroid rats, it was compared with that of the granule cells which were labeled after a pulse of [ 3H]thymidine at various stages of development. It appeared that the localization of the dying cells corresponded roughly to that of granule cells labeled on day 9. Therefore the maximum time required for granule cell death was about 5 days. Since the migratory phase through the molecular layer lasted about two days, the granule cells died after a maximum time of 3 days following their deposition in the internal granular layer. Information concerning the time of survival of the dying granule cells was important for subsequent investigation of the mechanisms underlying increased granule cell death in the hypothyroid cerebellum and the corrective effects of thyroid hormone.

Lysosomal behavior during lateral motor column neurogenesis

Modulations in the total and free activities of acid phosphatase, acid protease, aryl sulfatase, and β-glucuronidase reveal that maximum lysosomal activity accompanies histogenetic cell death within the lateral motor column (LMC) of Rana pipiens larvae. LMC neurogenesis is separable into three distinct periods. In the first, hydrolytic activity remains low through the initial half of the period only to exhibit an exponential rise in the latter half. This increase in acid hydrolase activity continues well into the period of histogenetic cell death (Period 2). At this juncture, lysosomal activity (total and free) reaches a maximum. Subsequently, hydrolytic activity declines with the cessation of neuronal death (Period 3). Activation experiments indicate that lysosomal granules isolated during the cell death period are extremely sensitive to a variety of procedures which disrupt membranes, whereas preparations from younger or older larvae are more stable. Alterations in lysosomal properties are discussed in terms of our present knowledge on lysosomal packaging, activation, and heterogeneity during the course of neural maturation.

Morphological cell death in the post-embryonic development of the insect optic lobes.

THE incidence of cell death among differentiating cells of the embryonic vertebrate central nervous system is well documented1–3, and there is evidence that in some cases its occurrence is influenced by the peripheral load encountered by the outgrowing fibres1–5. In vertebrate neural ontogeny both morphogenetic and histogenetic cell death have been observed6,7. Histogenetic cell death—which is involved in the differentiation of organs and tissues—has also been reported in the embryonic nervous systems of insects, for example, Tenebrio8 and the gall midge, Miastor (personal communication from S. Counce). It is reported here in the post-embryonically developing optic lobes of the larval and pupal brains of the endopterygote Danaus plexippus L. (Lept.) and is of special interest because it is possible to determine the age of a particular cell in this region and to observe cell and fibre areas of a wide range of ages within the same individual (our unpublished results).