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Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog.

The cortex and basal ganglia are the major structures of the adult brain derived from the embryonic telencephalon. Two morphologically distinct regions of the basal ganglia are evident within the mature ventral telencephalon, the globus pallidus medially, and the striatum, which is positioned between the globus pallidus and the cortex. Deletion of the Sonic Hedgehog gene in mice indicates that this secreted signaling molecule is vital for the generation of both these ventral telencephalic regions. Previous experiments showed that Sonic Hedgehog induces differentiation of ventral neurons characteristic of the medial ganglionic eminence, the embryonic structure which gives rise to the globus pallidus. In this paper, we show that later in development, Sonic Hedgehog induces ventral neurons with patterns of gene expression characteristic of the lateral ganglionic eminence. This is the embryonic structure from which the striatum is derived. These results suggest that temporally regulated changes in Sonic Hedgehog responsiveness are integral in the sequential induction of basal telencephalic structures.

Animals↗

Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum.

The telencephalon is organized into distinct longitudinal domains: the cerebral cortex and the basal ganglia. The basal ganglia primarily consists of a dorsal region (striatum) and a ventral region (pallidum). Within the telencephalon, the anlage of the pallidum expresses the Nkx2.1 homeobox gene. A mouse deficient in Nkx2.1 function does not form pallidal structures, lacks basal forebrain TrkA-positive neurons (probable cholinergic neurons) and has reduced numbers of cortical cells expressing GABA, DLX2 and calbindin that migrate from the pallidum through the striatum and into the cortex. We present evidence that these phenotypes result from a ventral-to-dorsal transformation of the pallidal primordium into a striatal-like anlage.

Animals↗

Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon.

In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern. We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions. They first appear within a region of anterior hypothalamic neuroepithelium that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex. Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HH) signalling is obligatory for oligodendrogenesis in the ventral telencephalon. Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex. Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures. Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain.

Animals↗

Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon.

The telencephalon has two major subdivisions, the pallium and subpallium. The pallium, which primarily consists of glutamatergic cortical structures, expresses dorsal molecular markers, whereas the subpallium, which primarily consists of the GABAergic basal ganglia, expresses ventral molecular markers. Here, we present evidence that the progenitor and postmitotic cells flanking the pallial/subpallial boundary (PSB) in the embryonic mouse can be subdivided into multiple regions that express unique combinations of transcription factors. The domains that immediately flank the PSB are the ventral pallium (VP) and the dorsal lateral ganglionic eminence (dLGE). The early expression of the Pax6 and Gsh2 homeobox transcription factors overlaps in the region of the dLGE. Analyses of mice that lack functional alleles of either Gsh2 or Pax6 demonstrate that these genes have complementary roles in patterning the primordia flanking the PSB. In the Gsh2 mutants, the dLGE is respecified into a VP-like structure, whereas in the Pax6 mutants the VP is respecified into a dLGE-like structure. The role of Pax6 in dorsalizing the telencephalon is similar to its role in the spinal cord, supporting the hypothesis that some dorsoventral patterning mechanisms are used at all axial levels of the central nervous system.

Animals↗

EGFRs mediate chemotactic migration in the developing telencephalon.

Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.

Animals↗

A morphological study of the brain of Solea senegalensis. I. The telencephalon.

In this paper we present an anatomical description of the telencephalon of Solea senegalensis based on cresyl violet and haematoxilin-eosin-stained serial transverse sections. This work was conducted as a basis for the precise localization of neuroendocrine territories in the brain of a species with growing interest in marine aquaculture. The external asymmetric morphology of Senegalese sole is correlated with the asymmetry of the forebrain. The right olfactory nerve and bulb are larger than the contralateral ones and this asymmetry is also extended to the cerebral hemispheres. The olfactory bulb comprises an outer olfactory nerve fiber layer, a glomerular layer, an external cellular layer, a secondary olfactory fiber layer and an internal cellular layer. The telencephalic hemispheres can be divided in area dorsalis and area ventralis, consisting of eleven and eight cell masses, respectively. The area dorsalis comprises five subareas: a pars medialis (Dm), subdivided into four nuclei termed Dml to Dm4; a pars dorsalis (Dd); a pars lateralis (D1), which consists of dorsal (Dld), ventral (Dlv) and posterior (Dlp) subdivisions; a pars centralis (Dc); and more caudally, a pars posterioris (Dp), which is very prominent in this species. A nucleus taenia (NT) was observed in the transitional region between area dorsalis and area ventralis. The area ventralis consists of pars dorsalis (Vd), pars ventralis (Vv), pars supracommissuralis (Vs), pars postcommissuralis (Vp), pars lateralis (V1), pars centralis (Vc), pars intermedia (Vi) and nucleus entopeduncularis (E). A periventricular organ, that we have termed lateral septal organ (LSO), was observed in the ventral telencephalon, medial to Vv.

Animals↗

Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype.

The LIM homeodomain family of transcription factors is involved in many processes in the developing CNS, ranging from cell fate specification to connectivity. A member of this family of transcription factors, lhx6, is expressed in the medial ganglionic eminence (MGE) of the ventral telencephalon, where the vast majority of cortical interneurons are generated. Its expression in the GABA-containing MGE cells that migrate to the cortex suggests that this gene uniquely or in combination with other transcription factors may play a role in the neurochemical identity and migration of these neurons. We performed loss of function studies for lhx6 in mouse embryonic day 13.5 brain slices and dissociated MGE neuronal cultures using Lhx6-targeted small interfering RNA produced by a U6 promoter-driven vector. We found that silencing lhx6 impeded the tangential migration of interneurons into the cortex, although it did not obstruct their dispersion within the ganglionic eminence. Blocking lhx6 expression in dissociated MGE cultured neurons did not interfere with the production of GABA or its synthesizing enzyme. These results indicate that lhx6, unlike the closely related member lhx7, does not regulate neurotransmitter choice in interneurons but plays an important role in their migration from the ventral telencephalon to the neocortex.

Animals↗

Neuropeptide Y-immunoreactive structures in the telencephalon and diencephalon of the white sturgeon, Acipenser transmontanus, with special regard to the hypothalamo-hypophyseal system.

An immunohistochemical study using a streptavidin-biotin method demonstrated the extensive distribution of neuropeptide Y (NPY)-like immunoreactivity in the brain of the white sturgeon, Acipenser transmontanus, with the highest density in the basal telencephalon and diencephalon. Two labeled cell groups were found in the telencephalon, in mediobasal and dorsocaudal locations. Labeled fibers were considerably dense in the ventral area. The epithalamus displayed dense networks of varicose fibers in the ganglion habenulae, but only a few fibers were seen in the organon subcommissurale. In the thalamus, two groups of labeled cells were discerned in the periventricular gray matter: an anteroventral group largely composed of cerebrospinal fluid (CSF)-contacting neurons, and a dorsocaudal group consisting of non-CSF-contacting large neurons. The hypothalamus also contained a number of CSF-contacting neurons in the periventricular areas including the nucleus lobi inferioris, the nucleus lateralis tuberis and the nucleus recessus posterioris. Labeled varicose fibers were closely associated with the hypothalamo-hypophyseal complex, the organon vasculosum hypothalami, and the saccus vasculosus. Immunoreactive cells and fibers were also detected in the dorsal region of the adenohypophysis. These results suggest that NPY or a related molecule is involved in the hypothalamic neuroendocrine mechanisms of this primitive bony fish.

Animals↗

Development of the rat telencephalon--volumetric analysis.

With regard to intensive morphometric changes, morphometry as a method is mainly used for histogenetic studies of brain development in normal and experimental conditions. The aim of our study was to quantitatively analyse morphological parameters of the rat telencephalon during embryonic development. The investigation was carried out on semithin serial sections of rat brain from embryonic days 12 to 15. The volume densities (VV) of the lateral ventricles, the telencephalic neuroepithelium and the surrounding mesenchyme have been analysed stereologically and compared in examined embryonic stages. The neuroepithelial volume density was the smallest (28%) at E13 and the biggest (44%) at E15 (p<0.0005). The mesenchymal volume density was the smallest (32%) at E13 and the biggest (48%) at E14 (p<0.0005). The volume density of lateral ventricles was the biggest (40%) at E13 and the smallest (14%) at E15 (p<0.0005). Neurostereological methods have been making a very valuable contribution to neuroscience over recent years. We have used unbiased stereological counting methods to obtain objective quantitative parameters which show relations between some parts of rat embryonic telencephalon examined during its normal development.

Animals↗

[Effect of HSV-1 infection on the viability of the primary cultured chicken embryo telencephalon neurons].

OBJECTIVE: To observe the effect of HSV-1 infection on the viability of the cultured chicken embryo telencephalon neurons in vitro. METHODS: Primary culture model of chicken embryo of telencephalon neurons was established. Herpes simplex virus type 1 (HSV-1) was propagated in Vero cells and viral titer was measured by plaque forming method. Inverted microscope, transmission electron microscope, MTT cell viability and DNA agarose gels electrophoresis were used to evaluate the effect of HSV-1 infection on the neurons. RESULTS: At 24, 48, 72 hours post infection the viability of the neurons decreased by 25%, 56%, 97% as compared with the control group. Morphological changes and DNA agarose gel electrophoresis showed a necrotic effect. CONCLUSIONS: HSV-1 infection induced a remarkable decrease on the viability of neurons by necrosis rather than apoptosis.

Animals↗

[The production and distribution of the newborn neural precursor in the telencephalon of female Melanocorypha mongolica and compared with female Lonchura striata].

The production of labeled precursors in adult female Melanocorypha mongolica and Lonchura striata were investigated by using bromodeoxyuridine (BrdU) and ABC immunohistochemical method to mark new synthesized DNA. Then, the distribution of newborn precursor was compared between the two kinds of songbirds. The results reveal that: 1) During 1-4 days after BrdU intramuscular injection, there were a great number of labeled cells in lateral ventricular zone (LVZ),and forming proliferation 'hot spots' in the ventricular zone (VZ) of the ventral striatum and neostriatum. The newborn labeled precursor in the two adult songbirds originated from ventricular zone in telencephalon. In the two adult songbirds, there were a great number of labeled precursors in the ventricular zone (VZ) of the medial striatum and lateral striatum and forming proliferation 'the first hot spots'; in the top of LVZ and forming proliferation 'the second hot spots'. In Melanocorypha mongolica,there were a lot of labeled precursors in the tail of VZ in lateral striatum and forming proliferation 'the third hot spots'. But in Lonchura striata, there were a small number BrdU labeled precursors in the tail of VZ. 2) From 5 days after BrdU intramuscular injection in Melanocorypha mongolica, a great number of labeled precursors in the LVZ began to migrate into the other region of the telencephalon. During 5-30 day after BrdU intramuscular injection, some of labeled cells emerged into the nucleus of high vocal center (HVc), and robust nucleus of the archistriatum (RA) in Melanocorypha mongolica. But there were no BrdU labeled cells in the HVc and RA in female Lonchura striata during the 30 days after BrdU intramuscular injection. New neurons, which are added to HVc and RA continuously in adult female Melanocorypha mongolica, may be necessary for learning the new songs of adult male birds. HVc and RA of adult Lonchura striata have few new neurons to replace older neurons.

Animals↗

Transient calbindin-D28k-positive systems in the telencephalon: ganglionic eminence, developing striatum and cerebral cortex.

Calbindin-D28k (calbindin) is a member of the superfamily of calcium-binding proteins implicated in the regulation of intracellular calcium. In the mature brain, calbindin is widely expressed in neurons of the forebrain and the hindbrain, and in the telencephalon calbindin-like immunoreactivity is particularly strongly expressed by medium-sized neurons of the striatum and by certain other neurons in the cortex and subcortex. We have traced the development of calbindin expression in the forebrain of the rat, and report here that in addition to the steady development of these calbindin-positive neuronal systems, transient waves of calbindin expression occur in cells of the ventricular zones of the basal ganglia and cortex and in cells of the telencephalic regions derived from these ventricular zones including radial glia of the developing striatum. In the striatum and its ventricular zone (the ganglionic eminence, or GE) we identified four transient calbindin-positive systems in the perinatal period. First, calbindin-immunoreactive cells began to appear in the GE by embryonic day (E)18, and by E20 an extensive dorsal and lateral part of the GE was marked by dense calbindin-like immunoreactivity in the ventricular zone. This calbindin system peaked at postnatal day (P)0-P3 and disappeared by P15. Its presence suggests that the GE is divisible on a molecular basis into lateral and medial districts that may correspond to derivatives of the lateral and medial ventricular ridges. Second, a system of calbindin-positive processes appeared in the dorsal and lateral caudoputamen with temporal and spatial distributions matching the germinal zone system. Many of these processes could be traced from calbindin-positive cells in the ventricular zone of the GE, including processes stretching across the full width of the dorsal caudoputamen. Double-staining experiments demonstrated that these radial processes were Rat.401-positive, suggesting that they form a subset of radial glia in the developing telencephalon. These findings demonstrate that during development calbindin is expressed in glial as well as neural cells. They further suggest that the radial glia associated with the GE form heterogeneous populations, the transient calbindin-positive radial glia being associated with the lateral ridge of the GE and its derivatives. Third, a scattered population of calbindin-positive cells with morphologies different from the common medium-sized calbindin-immunoreactive neurons of the striatum appeared in the dorsal and lateral striatum from about E20 to P15. Some of these cells were close to the transient calbindin-positive radial processes in the same region, but others were not.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

[Efferent projections of "classical" peptidergic neurons of the neurosecretory system of the telencephalon in reptiles (Scincus scincus L. and Chalcides ocellatus Forskal; Lacertilia, Squamata].

In both species of lacertilian reptiles investigated, the peptidergic hypothalamic supraoptic and paraventricular nucleus project with efferents to the telencephalon, to caudal parts of the brain, and to the spinal cord. The marked system of efferents of the "classic" peptidergic neurosecretory nuclei to the telencephalon was mapped. The unlabeled peroxidase-antiperoxidase immunocytochemical procedure revealed at the light microscopical level neurophysin- respectively mesotocin- or vasotocin-containing exohypothalamic fibres in the septal area, in subcortical regions (ventral striatum and hypopallium), and in all layers of the cortical areas (medial, dorsal and lateral cortex). Within the different parts of the brain, there seems to be a characteristically quantitative ratio of the mesotocin and vasotocin fibres. The terminals of the exohypothalamic fibres contact perikarya and processes of neurons of the target regions intimately. In a selected area, peptidergic synapses could be demonstrated at the electron microscopical level using an ultrahistochemical method. It is assumed that the nonapeptides mentioned are released from the fibre terminals and then act as neurotransmitters/neuromodulators influencing different brain functions.

Animals↗

Neuronal migration and contact guidance in the primate telencephalon.

Over the last decade, evidence from experimental studies on neuronal migration in non-human primates has accumulated to the point where it can significantly amplify our understanding of the normal and pathological development of the human telencephalon. Systematic analysis of neuron genesis by the method of H3-thymidine autoradiography shows that in rhesus monkeys all neurons destined for the neocortex are generated near the surface of the lateral ventricle during a two-month period in the middle of gestation. Following their last cell division, young neurons migrate outwards across the cerebral wall to the developing cortical mantle, a journey that requires one to three days at early stages of neurogenesis, or more than two weeks towards the end of cortical development. From the very beginning, the basic columnar organization of the neuroepithelium favours radial migration. During later stages, when the primate telencephalic wall expands unevenly in thickness and surface area and begins to form primary fissures and cerebral promontoria, young neurons migrate to their cortical destinations in apposition to fascicles of radial glial fibres which span the full distance between the ventricular and pial surface. Furthermore, it appears that several generations of neurons all originate in the same restricted location at the ventricular surface, migrate along the same glial fascicles and consequently accumulate in the same radial cortical 'columns' in which, as a rule, somas of later generated neurons take positions external to the somas of their predecessors. It is proposed that fascicles of radial fibres (a) facilitate neuronal migration to the distant cortical plate through a complex assembly of closely-packed cells and processes that compose the developing primate telencephalon; (b) provide constraints which preserve a radial alignment of clonally related neurons in cortical columns; and (c) reproduce the mosaicism of the germinal ventricular zone at the expanded and curved cerebral surface.

Animals↗

Volumetric development of the fetal telencephalon, cerebral cortex, diencephalon, and rhombencephalon including the cerebellum in man.

Fresh volumes of the human telencephalon, cerebral cortex, diencephalon, and of the rhombencephalon including cerebellum were determined in a series of 10 normal specimens ranging in age from 63 to 176 days after conception. The volumetric growth of these parts shows a nonlinear dependence on age with a smaller increase during the 3d ontogenetic month and a stronger increase from the 4th month on. These data were analyzed together with previous measurements of 28 brains taken from the Yakovlev Collection in Washington, D.C., and the Vogt Collection in Düsseldorf. These brains range in age from 137 to 22,900 days after conception. These samples were reproduced in a model using sigmoid logistic functions. The entire brain and all analyzed parts show a monotonous growth. The individual regions develop heterochronously. The diencephalon is the first part to reach its ideal volume, with a main growth spurt between 100 and 420 days after conception. The rhombencephalon including the cerebellum is the last, with its main growth spurt between 240 and 650 days after conception. The growth of the entire brain is determined to a great extent by that of the telencephalon, having a main growth spurt between 175 and 580 days after conception. The prenatal growth is described separately with the asymmetric sigmoid function according to Gompertz. This yields a better approximation of the data collected from the early prenatal period.

Cerebellum↗

Regional distribution of muscarinic acetylcholine receptors in the telencephalon of the pigeon (Columbia livia f. domestica).

The distribution of muscarinic ACh receptors was studied autoradiographically in cryostat sections of the pigeon telencephalon using 3H-Quinuclidinylbenzylate (QNB) as a ligand. Highest receptor density was observed in the hyperstriatum ventrale, palaeostriatum augmentatum, septum, and parts of the archistriatum In sites of known sensory input of neostriatum (field L) and ectostriatum low receptor binding was observed. Acetylcholinesterase distribution is in good agreement with the receptor picture only in the basal telencephalon. In the pallium differences in the pattern of these two components can be seen.

Animals↗

Response of the regenerating telencephalon of Lacerta viridis to nerve growth factor.

To identify the nature of the dividing cells during the regenerative process of the telencephalon, the authors administered nerve growth factor (NGF) to Lacerta viridis with a wedge of telencephalon removed. Some known centers of cell proliferation were unresponsive to the treatment, whereas the ventral end of the telencephalic ventricle underwent an increase of up to 200% in proliferation rate. On the basis of this observation and data in the literature, the authors propose that the cell proliferation beginning in the medial area during the regeneration of the telencephalic ventricle is due to catecholaminergic neuroblasts still present in the adult.

Animals↗

[Anatomical study of the afferent pathways of the rostral telencephalon in the Gallus domesticus chick].

The neuroanatomical method involving retrograde axonal transport of horseradish peroxidase (HRP) was employed in the chick Gallus domesticus to investigate ascending projection systems to the rostral telencephalon. Following either extensive or restricted injections of the enzyme into different regions of the latter, differential bilateral or unilateral projections onto the Wulst (hyperstriatum accessorium, hyperstriatum intercalatus superior, hyperstriatum dorsale) were demonstrated from the dorsal thalami complex (nucleus dorsolateralis anterior thalami, pars lateralis). Other nuclei of the dorsal thalamus shown to project to the rostral telencephalon were nuclei, dorsolateralis medialis, dorsolateralis posterior, dorsomedialis anterior, parvocellularis and rotundus. At the level of the mesencephalon, rostral telencephalic projections were found to originate in the substantia grisea centralis, the strata cellulare externum and internum, the lateral reticular formation and the area ventralis. More caudally peroxidase label was localized in the nuclei locus, ceruleus, subceruleus dorsale, subceruleus ventrale and within the principal Vth nucleus. The results obtained using restricted injections of HRP made it possible to more precisely identify the telencephalic projections sites of several of the above areas and nuclei. The data is compared to previous findings regarding ascending projection system in different avian species and some methodological problems in the use of HRP technique are discussed.

Afferent Pathways↗