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At least 19 recordsLinked to original sources

PubMed1976

Neurogenesis in the visual system of the rat. An autoradiographic investigation.

Rats of the BD III strain were injected with a single dose of 3H-thymidine on either the twelfth, fourteenth, sixteenth, eighteenth or twentieth day of gestation (ED 12. . . . .ED 20) or on the postnatal day one, three, or seven. Animals were killed at age 22 to 24 days. DNA synthesis, as an indicator of cell division, was studied in matrix precursors of nerve and glial cells in the visula centers, including the lateral geniculate body (LGB), the superior colliculus (SC) and the visual cortex (VC). It was found that proliferation of matrix precursors of nerve cells destined for all the regions studied was in progress on ED 12. In the subcortical regions (LGB, SC) this process was substantially more advanced than in the VC. The first neuroblasts appeared in the SC (ED 12) and only later (ED 14) in the LGB and VC. In comparison with the LGB, VC neuroblasts were quite rare on ED 14 and were present only in layer VI. They appeared more frequently in this region only after injection of isotope on ED 16. Matrix cell proliferation and nerve cell formation ceased in the LGB between ED 16 and ED 18. The number of labeled cells arising after injection of the isotope on ED 16 indicates that neurogenesis ceased somewhat earlier in the dorsal nucleus of the LGB than in the ventral. In the SC the last neurons arose between ED 18 and ED 20, and in the VC, with the possible exception of a few granular neurons (which may continue division into the first few days postnatally), proliferation continued until the end of gestation. The origin of neuroblasts initially followed a caudo-rostral gradient. Later, the times of neurogenesis in the regions studied overlapped significantly. This is clear, for example. on ED 16, when neurogenesis in the mesencephalic SC continued for about two days longer than in the more postral LGB, and coincided with that in the VC, especially in the deep layers. The end of neurogenesis in the LGB, especially in the ventral nucleus, coincided with the time of neurogenesis in the deep cortical layers. In the VC, and partly also in the SC, an inside-out pattern of proliferation and neuron formation was confirmed. The times of proliferation of precursor cells, with the exception of the very end of neurogenesis, substantially overlapped within both these regions. The degree of this overlapping, described in terms of Labeling Index values, decreased towards the end of the neurogenetic period. Division of neuroglial cell precursors, started as early as on ED 14 in/for subcortical centers (LGB, SC), but not until ED 18 in/for the VC. A few labeled endothelial-like cells were observed in all regions studied after isotope injection on ED 12.

Age Factors↗

PubMed1991

Neurogenesis in the brain auditory pathway of a marsupial, the northern native cat (Dasyurus hallucatus).

Neurogenesis in the auditory pathway of the marsupial Dasyurus hallucatus was studied. Intraperitoneal injections of tritiated thymidine (20-40 microCi) were made into pouch-young varying from 1 to 56 days pouch-life. Animals were killed as adults and brain sections were prepared for autoradiography and counterstained with a Nissl stain. Neurons in the ventral cochlear nucleus were generated prior to 3 days pouch-life, in the superior olive at 5-7 days, and in the dorsal cochlear nucleus over a prolonged period. Inferior collicular neurogenesis lagged behind that in the medial geniculate, the latter taking place between days 3 and 9 and the former between days 7 and 22. Neurogenesis began in the auditory cortex on day 9 and was completed by about day 42. Thus neurogenesis was complete in the medullary auditory nuclei before that in the midbrain commenced, and in the medial geniculate before that in the auditory cortex commenced. The time course of neurogenesis in the auditory pathway of the native cat was very similar to that in another marsupial, the brushtail possum. For both, neurogenesis occurred earlier than in eutherian mammals of a similar size but was more protracted.

Aging↗

PubMed1990

Gradients of neurogenesis in possum neocortex.

Gradients of neurogenesis in neocortex of the brushtailed possum were determined with [3H]thymidine autoradiography, using data taken from 16 possums injected with [3H]thymidine between postnatal (P) days 5-68, and allowed to survive until brain cytoarchitecture was mature. Gradients of neurogenesis shown in neocortex were: (a) an inside-out radial gradient within cortical areas with neurogenesis beginning around P5 in layer 6 and concluding between 1 and 2 months later in layer 2, and (b) a single, simple, regional gradient across all neocortex. On the lateral surface of the hemisphere neurogenesis runs anteroventrolateral to posterodorsomedial, and on the medial surface neurogenesis runs anteroventral to posterodorsal. When plotted for the whole neocortex, the two regional gradients from the lateral and medial surfaces of the hemisphere are seen as parts of the one simple pattern. The time duration of neurogenesis in possum cortex is 1-2 months, and is similar to that seen in monkeys.

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PubMed1989

Neurogenesis of glutamic acid decarboxylase immunoreactive cells in the hippocampus of the mouse. II: Area dentata.

The temporal patterns of neurogenesis of cells showing glutamic acid decarboxylase (GAD) immunoreactivity were determined in the area dentata of the mouse. Pregnant C57Bl mice received pulse injections of (3H)thymidine from E11 through E17 (E0 being the day of mating). The distribution of (3H)thymidine-labeled, GAD-positive neurons in the hilus and in the different strata of the fascia dentata (stratum infragranulosum, stratum granulosum, stratum moleculare) were recorded in adult animals. A radial gradient of neurogenesis of GAD-positive cells in the area dentata was not apparent. In the transverse axis, neurogenesis of GAD-positive cells seemed to follow a faint suprapyramidal to infrapyramidal gradient, which was due to differential timing of neurogenesis of GAD-positive cells destined for the stratum infragranulosum of the suprapyramidal and infrapyramidal blades of the fascia dentata. GABAergic neurons in the fascia dentata comprise a limited number of well-defined cell types. All of the different morphologic types of GAD-positive neurons present in the area dentata were generated prenatally. These diverse forms did not have specific times of neurogenesis. These results support the concept that the adult morphology of GAD-positive cells in the area dentata of the mouse do not bear any relationship to their times of origin.

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PubMed2016

Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

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PubMed1990

Neurogenesis of the magnocellular basal forebrain nuclei in the rhesus monkey.

The time of origin of the neurons that comprise the magnocellular basal forebrain nuclei in rhesus monkeys was determined by using [3H]thymidine autoradiography. Thirteen pregnant animals received an injection of [3H]thymidine between embryonic days 27 (E27) and E50 of their 165 day gestation, and their offspring were sacrificed during the early postnatal period. Neurons within this region were generated in a biphasic pattern. An initial burst of [3H]thymidine-labeled magnocellular neurons was first observed throughout short quiescent period, cells of the remaining anterior basal forebrain (inclusive of magnocellular neurons comprising the vertical limb of the diagonal band and the anteromedial and anterolateral regions of the nucleus basalis) were generated between E36 and E45 with a peak of neurogenesis seen on E40-E43. The intermediate division of the nucleus basalis was generated about the same time, but the peak period of neurogenesis in this region occurred slightly earlier (E36 and E40) and was completed by E43. During the second phase of neurogenesis, neurons within the posterior division of the basal forebrain were generated first, with their genesis virtually completed between E33 and E36. The genesis of all neurons comprising the magnocellular basal forebrain nuclei was completed by E48 of gestation. A general caudal to rostral gradient of neurogenesis was observed within this telencephalic region. In contrast, a neurogenic gradient was not discerned in the radial direction. The present data demonstrate that neurons comprising the basal forebrain magnocellular nuclei in monkeys are generated early in gestation with two peak times of neuronal genesis. These nuclei are among the earliest to be generated in the entire telencephalon, which, like neurons of the thalamus and cortical neurons giving rise to cortical-cortical connections, places them in a strategic position to potentially influence their target neurons within the cortical mantle that are generated later in gestation.

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PubMed1990

Neurogenesis of the hamster suprachiasmatic nucleus.

Neurogenesis of the hypothalamic suprachiasmatic nucleus (SCN) was described in the Syrian hamster (Mesocricetus auratus) using tritiated [3H]thymidine autoradiography. Pregnant hamsters were given single intraperitoneal injections of [3H]thymidine at different times during prenatal development, and labeled cells were analyzed in the offspring of 4-5 weeks of age. Cells of the hamster SCN became postmitotic (were 'born') over two and a half days from 10.5 to 13.0 days postfertilization (dpf) with a peak around 11.5 dpf, 4 days before birth. Two gradients in SCN neurogenesis were observed. Posterior cells were produced somewhat earlier than anterior cells and ventrolateral cells were produced before dorsomedial cells. An exception to the second gradient was a small population of ventrolateral cells produced near the end of SCN neurogenesis. The pattern of SCN neurogenesis in the hamster was similar to that described in the rat, including a predominant ventrolateral to dorsomedial gradient and the presence of ventral or ventrolateral cells produced relatively late, contrary to the predominant gradient.

Aging↗

PubMed1989

Neurogenesis of basal forebrain cholinergic neurons in rat.

The basal forebrain cholinergic system embodies a heterogeneous group of neurons distributed in the basal telencephalon that project topographically to the cortical mantle. We sought to examine the generation of these neurons to determine whether basal forebrain neurons have unique patterns of neurogenesis or, if, in contrast, they are born along general neurogenic gradients. The techniques of tritiated thymidine autoradiography and choline acetyltransferase (ChAT) immunocytochemistry were combined to determine the birthdays and neurogenic gradients of cholinergic cells in this region of rat brain. Cholinergic neurogenesis throughout the basal forebrain ranged from embryonic days 12 to 17 (E12-17). Neurogenesis in the nucleus basalis magnocellularis occurred over E12-16, with a peak day of generation on E13. The horizontal limb nucleus of the diagonal band which is located rostral to the nucleus basalis was generated over E12-17, with the majority of cells arising on E14-15. The rostral-most nuclei of the basal forebrain cholinergic system, the vertical limb of the diagonal band and the medial septum, were generated between E13-17, with peak days of neurogenesis on E15 and E15-16, respectively. These results were evaluated quantitatively and demonstrated that the basal forebrain cholinergic neurons were generated along the general caudal-to-rostral gradient previously described for all neurons in this brain region. The results of this study, in combination with those of similar investigations, emphasize that position-dependent epigenetic factors appear to be more potent determinants of the time of neuronal origin than factors which influence a cell's transmitter phenotype.

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PubMed1992

Neurogenesis of the amygdaloid nuclear complex in the rhesus monkey.

The time course of neurogenesis for neurons which comprise the amygdaloid complex in Rhesus monkeys was determined using tritiated thymidine autoradiography. Fourteen pregnant monkeys received injections of tritiated thymidine between embryonic days 27 (E27) and 56 of their 165 day gestation and offspring were sacrificed during the early postnatal period. The first neurons destined for the amygdaloid complex were generated at E33 making them among the earliest postmitotic neurons in the telencephalon. Neurogenesis peaked within all nuclei of the amygdaloid complex between E38 and E48 and had ceased between E50 and E56. While amygdaloid neurogenesis in postnatally sacrificed monkeys displayed a dorsal-to-ventral gradient of radiolabeled neurons, the considerable rotation of the temporal lobe during the latter stages of primate development indicates that neurogenesis in the embryo, during the first third of gestation, actually occurs across a medial-to-lateral gradient. This medial-to-lateral gradient occurs as a smooth wave across the amygdaloid nuclei and does not respect neuroanatomical subdivisions or patterns of connectivity of the amygdaloid nuclei in the Rhesus monkey.

Amygdala↗

PubMed1991

Regulation of neurogenesis and neuronal differentiation in primary and immortalized cells from mouse olfactory epithelium.

We have developed an in vitro system for studying molecular events regulating neurogenesis in the mouse olfactory epithelium (OE). Our observations suggest that two types of neuronal precursor may be involved: (1) a transiently existing, immediate neuronal precursor (INP), which generates two postmitotic daughter neurons; and (2) a neuroepithelial stem cell, which may be the basal cell (or some subclass of basal cell) of the OE, and is presumed to be the progenitor of the INP. Using antibody markers that distinguish basal cells and postmitotic receptor neurons in vitro and in vivo, we have shown that neurogenesis occurs early on in OE cultures, but then ceases because INPs divide only once to generate postmitotic neurons and no new INPs are produced by basal cells. To determine whether the basal cell-to-INP transition, or proliferation and neuronal differentiation of the INP, are regulated by crucial growth factors or cellular interactions, we are testing various polypeptide growth factors and extracellular matrix proteins for their effects on OE neurogenesis in vitro. We have also generated immortalized OE cell lines by using retroviruses to transduce oncogenes into cultured OE cells. One such cell line (derived from a primary OE basal cell culture) develops branching processes when transplanted into neonatal mouse brain--a condition in which cells from freshly isolated OE can undergo apparent morphological differentiation into neurons.

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PubMed1989

Neurogenesis of glutamic acid decarboxylase immunoreactive cells in the hippocampus of the mouse. I: Regio superior and regio inferior.

The neurogenetic gradients of neurons showing glutamic acid decarboxylase (GAD) immunoreactivity were determined in the regio superior and in the regio inferior of the mouse hippocampus. Pregnant C57Bl mice received pulse injections of (3H)thymidine from E11 through E17 (E0 being the day of mating). Distributions of (3H)thymidine-labeled, GAD-positive neurons in the different strata of the hippocampus proper were recorded in adult animals. GAD-positive neurons in this region are generated prenatally. Radial gradients of neurogenesis of GAD-positive cells are characterized by two main features: 1) with the exception of the stratum lacunosum-moleculare and its interface with the stratum radiatum, GAD-positive neurons of the plexiform strata are generated before those destined for the pyramidal layer; 2) within the pyramidal layer, GAD-positive cells are positioned according to an inside-out sequence. In the transverse axis, neurogenesis of GAD-positive cells follows a regio inferior to regio superior gradient. This gradient is due to prolonged neurogenesis of GAD-positive cells for the pyramidal layer in the regio superior. Given the selective laminar disposition of the GABAergic interneurons in the hippocampus, the present authors explored whether or not the diverse types of these interneurons could have specific birth dates and concluded that no relationship exists between birth dates and adult phenotypes of GAD-immunoreactive cells in the mouse hippocampus proper.

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PubMed1990

Mechanism of neurogenesis in adult avian brain.

Adult neurogenesis in birds offers unique opportunities to study basic questions addressing the birth, migration and differentiation of neurons. Neurons in adult canaries originate from discrete proliferative regions on the walls of the lateral ventricles. They migrate away from their site of birth, initially at high rates, along the processes of radical cells. The rates of dispersal diminish as the young neurons invade regions devoid of radial fibers, probably under the guidance of other cues. The discrete sites of birth in the ventricular zone generate neurons that end up differentiating throughout the telencephalon. New neurons may become interneurons or projection neurons; the latter connect two song control nuclei between neostriatum and archistriatum. Radial cells, that in mammals disappear as neurogenesis comes to an end, persist in the adult avian brain. The presence of radial cells may be key to adult neurogenesis. Not only do they serve as guides for initial dispersal, they also divide and may be the progenitors of new neurons.

Animals↗

PubMed1989

Neurogenesis of the basal forebrain in euploid and trisomy 16 mice: an animal model for developmental disorders in Down syndrome.

The neurogenesis and early histochemical differentiation of the basal forebrain in trisomy 16 fetal mice and their euploid littermates were examined by combining [3H]thymidine autoradiography with acetylcholinesterase histochemistry. Neurons of the basal forebrain were being born between embryonic day 11 and 15 in both chromosomally normal (euploid) and aneuploid mice. In euploid littermate controls, neurogenesis proceeded along a caudal to rostral gradient with the peak on embryonic day 11 for caudal portions and embryonic day 13 for rostral portions of the basal forebrain. In contrast, in trisomy 16 mice, rostral sections exhibited a peak of neurogenesis on embryonic day 11, 2 days earlier than in their euploid littermate controls. Hypocellularity of the basal forebrain region was noted in trisomy 16 mice; particularly dramatic was the reduction of the population of cells that expressed acetylcholinesterase. This reduction in cell number in the trisomics was not accompanied by a reduction in cell size or by a dramatic change in the distribution of residual neurons when compared to that of euploid littermate controls. Since trisomy 16 mice do not survive the perinatal period, we examined the pattern of acetylcholinesterase expression in normal C57B1/6J mice from embryonic day 16 to postnatal day 5 to determine the postnatal disposition of these neurons. Already at embryonic day 16, fibers staining for acetylcholinesterase penetrated the striatal anlage, in their course towards targets in the cerebral cortices. By postnatal day 5, the previously expansive distribution of basal forebrain neurons had become consolidated in a more ventral and rostral position by the extensive outgrowth of the striatal neurons, a pattern resembling that seen in adult animals.

Acetylcholinesterase↗

PubMed1990

Neurogenesis and development of callosal and intracortical connections in the hamster.

The developmental time-course of callosal and ipsilateral corticocortical projections was studied in embryonic and postnatal hamsters, from the time of neurogenesis until the appearance of adult patterns. Callosal neurogenesis was determined by combining the incorporation of [3H]thymidine injected on specific embryonic days with retrograde labelling of callosal neurons in the adult animal. The development of both callosal and corticocortical projections was studied by the transport of wheat germ agglutinin conjugated to horseradish peroxidase. Despite a significant radial disperson of postmigratory neurons born on the same day, it was found that the birthdates of callosally-projecting neurons in the frontal cortex were not restricted to a short period of time, but extended between embryonic days 13 and 15. This period covers the neurogenesis of cells in cortical layers III-V. Elongation of callosal axons (and possibly also of corticocortical fibres) started a couple of days before birth in the frontal cortex, and continued through the first postnatal days. After a "waiting period" of a few days, axons from both sets of projections were seen innervating restricted target sectors of the cortex. The zones of origin of these projections were initially exuberant, but were subsequently trimmed to overlap completely with the corresponding terminal fields. It is concluded that callosal and ipsilateral corticocortical projections undergo similar sequences of ontogenetic stages, suggesting that the development of neocortical connectivity as a whole may be governed by one and the same set of rules.

Animals↗

PubMed1989

Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro.

Development of a culture system for mammalian olfactory epithelium has permitted the process of neurogenesis to be examined in vitro. Antibody markers allowing the unambiguous identification of putative neuroepithelial stem cells (keratin+ basal cells) and differentiated neurons (N-CAM+ olfactory receptor neurons) are described. In combination with [3H]thymidine uptake analysis, these antibodies have been used to characterize the existence, proliferation, and differentiation of the immediate neuronal precursor in this system. This cell is distinct from basal cells and rapidly sorts out from them, dividing as it migrates. Data are presented which suggest that the precursor follows a simple lineage program, dividing to give rise to two N-CAM+ daughter neurons. Although this precursor efficiently generates neurons in defined medium, neurogenesis subsequently ceases because new precursors are not produced, suggesting that epigenetic factors may regulate continual neurogenesis in this system.

Animals↗

PubMed1992

In vitro neurogenesis by neuronal precursor cells derived from the adult songbird brain.

The vocal control nucleus of the adult songbird forebrain, HVc, exhibits de novo neurogenesis in adulthood, with the production of new neurons from precursor cells located in the overlying ventricular zone (Goldman and Nottebohm, 1983). We previously established that explants derived from neurogenic regions of the adult canary forebrain could be maintained in vitro, under conditions that permitted the migration and differentiation of those new neurons previously generated in vivo (Goldman, 1990). However, we found no evidence for continued neuronal mitogenesis in these cultures, which were raised in high concentrations of serum. In the present study, we investigated the permissive conditions for in vitro neurogenesis by these adult forebrain-derived ventricular zone explants. When HVc explants derived from adult zebra finches were maintained in low-serum medium, in vitro neurogenesis could be demonstrated by 3H-thymidine uptake as long as 5 days after explantation. Immunocytochemistry for microtubule-associated protein-2 followed by autoradiography confirmed the neuronal identity of these 3H-thymidine-incorporating cells. In vitro neuronal production occurred in an inverse relation to the serum concentration: Over the range of 2.5-25% fetal bovine serum, neuronal 3H-thymidine labeling was most frequent in those cultures exposed to the lowest serum levels. This facilitation of in vitro neuronal mitogenesis by serum depletion suggests that fetal serum may contain factors that inhibit the division of adult-derived neuronal precursor cells, either directly or by agents released by serum-stimulated glial or ependymal cells.

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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.

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PubMed1977

Neurogenesis in the epithalamus, dorsal thalamus and ventral thalamus of the rat: an autoradiographic and cytological study.

Times of final mitotic division for neurons of the epithalamic, dorsal thalamic and subthalamic nuclei of the rat were determined with the aid of thymidine-H3 autoradiography. Intensely labelled neurons were observed in the brains of animals injected with radiochemical from days 13 to 19 of gestation. The pattern of distribution of the labelled neurons indicated that neurogenesis in the regions followed caudorostral, lateromedial and ventrodorsal neurogenetic gradients, all of which were found to operate simultaneously. Since neurogenesis in the epithalamus, subthalamus and caudolateral thalamic regions began on days 13 and 14 of gestation, the ventrodorsal and lateromedial proliferative gradients were clearly discerned only within the ventral and dorsal thalamus exclusive of the epithalamus. These directional neurogenetic gradients were apparent throughout the entire thalamus and within individual thalamic nuclei. No neurogenetic pattern based upon neuronal size was observed, i.e., large neurons were not preferentially formed earlier than smaller ones. Detailed information has also been provided on the cytological character of each thalamic nucleus.

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