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Fibroblast growth factor 2 increases Otx2 expression in precursor cells from mammalian telencephalon.

Dissociated primary cultures from rat telencephalon at different developmental stages were used to study the effect of basic fibroblast growth factor (FGF2) on Otx2, Dlx1, and Emx1, three homeobox genes expressed in different regions of the developing mammalian forebrain. At embryonic day (E)13.5. the regional pattern of expression of Otx1, Otx2, Dlx1, Dlx2, Dlx5, and Emx1 is maintained in primary culture, suggesting that cells are already committed to a regional identity at this stage. In these cultures, Otx2 is expressed by precursor cells, whereas Dlx1 and Emx1 are predominantly expressed by postmitotic cells. We found that FGF2 increased Otx2 expression within precursor cells and the total number of Otx2-expressing cells. This effect was gene-specific, dose-dependent, and temporally regulated, with larger effects at earlier stages of development (E11.5). At E13.5, the effect of FGF2 on Otx2 expression was restricted to the basal telencephalon. Our results suggest that a restricted population of neuroblasts respond to FGF2 in a temporally regulated fashion by proliferating and increasing Otx2 expression. This interaction between FGF2 and Otx2 may be important for the regulation of neurogenesis in the forebrain.

Animals↗

Evaluation of human telencephalon microangioarchitecture in fetal period.

The aim of the work was to examine internal vascularization of telencephalon. The brains of 200 fetuses aged 3-8 months of fetal life were examined. Various techniques were used: injection, infrared, Pickworht's method, image computer transformation. Linear and non-linear transformations (mathematical morphology) were also used. The five vascular layers of telencephalon were distinguished: cortical, of white matter, striatal, germinal and of choroid plexus. Their morphology and changes occurring in fetal period were estimated. It was observed that subcortical and paraventricular regions belong to hypovascular areas. White matter vessels were seen as rectilinear without any ramifications. After 6 months of fetal life the most intensive development of inner cerebral vessels occurs. Two age groups were distinguished. The first one comprises the period of 4th to 6th month and is characterized by the existence of long medullary and abundant germinal matrix vessels. The second group (over 7th months) may be described as intensive development of cortical vessels.

Electronic Data Processing↗

Vascularization of the brain in guinea pig. V. Angioarchitectonics of the thalamus, telencephalon and internal capsule.

The main blood supply of the thalamus constitute internal branches of the posterior cerebral, posterior communicating, middle, and choroid arteries. Branches of these arteries from three groups of vessels: medial, lateral, and posterior. Considering the number of vessels, their diameter and direct origin from the cerebral arterial circle, the thalamus is best vascularized structure of the brain. The telencephalon is supplied by rami of the anterior and middle cerebral, choroid, posterior communicating, and posterior cerebral arteries. The internal capsule and telencephalic nuclei are supplied by the internal branches of the same vessels as the telencephalon as well as by the cortical rami of the middle and posterior cerebral arteries. All these vessels from anteromedial, anterolateral, and superolateral groups. Between the internal and cortical branches anastomotic vessels are seen.

Animals↗

Astroglia-microvessel relationship in the developing human telencephalon.

The telencephalon of 12 and 18 week-old human foetuses was examined for evidence of astroglia-microvessel relationship. Immature astroglia cells (radial glia and astroblasts) and astrocytes were immunostained using antibodies to the cytoskeletal proteins vimentin (VIM) and glial fibrillary acidic protein (GFAP). The microvessels were detected using an antibody to the blood-brain barrier (BBB)-specific glucose transporter GLUT1. Two extracellular matrix (ECM) glycoproteins, laminin (LM), an endothelial-derived molecule, and tenascin-C (TN-C), a glia-derived molecule, were also analyzed. In the two stages examined, VIM- and GFAP-positive fibers of the radial glia establish close relationships with the radial and periventricular microvessels, which are GLUT1-positive and lined by an LM-positive basal lamina-like matrix. At the 18th week, also radial glia transitional forms and immature astrocytes exhibit extensive contacts with the microvasculature. A TN-C-rich ECM is revealed around the vascular plexus of ventricular zones at the 12th week, and around the newly growing radial microvessels and the microvessel branching sites at the 18th week. The observations taken as a whole, suggest that during the telencephalon morphogenesis the immature astroglia cells play a role in the early establishment of the distribution pattern of the neural microvessels and in their growth and maturation.

Abortion, Spontaneous↗

Auditory topography and temporal response dynamics of canary caudal telencephalon.

To map the encoding of auditory cues in songbirds, multiunit electrophysiological responses to pure tone stimuli (250-5000 Hz) were recorded at 373 sites throughout the avian analogue of the mammalian auditory cortex in the caudal telencephalon of awake, restrained canaries. We found that a dorso-ventral tonotopic gradient from low to high frequency stimuli extends from the rostral field L2 to caudal-most caudo-medial nidopallium (NCM), similar to the frequency-dependent patterns of ZENK gene expression in canary NCM and to electrophysiological responses in other songbird species. However, response characteristics differ across the region. In field L2, responses are vigorous, phasic, and do not habituate to repeated presentations of the same stimulus. In an important subset of field L2 sites, tuning width narrows over the course of the response, which then terminates rapidly at stimulus offset. These properties are associated with inhibition at many nonpreferred frequencies and poststimulus inhibition at responsive frequencies. In contrast, NCM sites habituate to repeated sine waves, have wider tuning and lower amplitude responses, and rarely show inhibitory effects. Tuning curves in NCM are also flatter than those of field L2, and are often multipeaked. In addition, tuning width increases as the response unfolds and poststimulus excitation is often sustained in NCM. In sum, specific parts of the canary caudo-medial telencephalon differ in their response properties, suggesting differential roles in auditory processing. NCM properties, in particular, may allow for response integration across multiple spectrally varying stimulus elements, such as those that occur during birdsong.

Acoustic Stimulation↗

A study of the potential of the embryonic rat telencephalon to generate oligodendrocytes.

A major question in neural development is whether each part of the telencephalon has an equal potential to generate each cell type. In this study, we address this question specifically in regard to the generation of oligodendrocytes. We cultured precursor cells from two different regions of the rat embryonic telencephalon--the ganglionic eminence that the anlage of the cerebral cortex--from different stages of development, and labeled the cells with a retroviral vector to follow their fate. We discovered that multipotential precursor cells from E13 ganglionic eminence have several orders of magnitude higher capacity to generate oligodendrocyte than the equivalent cells from E13 cerebral cortex. This failure of cortical precursor cells to generate oligodendrocytes at early development stages (E12-E13) could not be reversed by growth factors, permissive growth media, or a permissive striatal cell environment. A combination of striatal contact and plus specific growth factors, however, did induce the production of oligodendrocytes. We conclude that telencephalic precursor cells do not have the potential to generate oligodendrocytes, but that this potential is significantly greater in striatal than cortical multipotential precursor cells.

Animals↗

Formaldehyde-induced fluorescence in the telencephalon and diencephalon of the eel (Anguilla anguilla l.). A fluorescence-microscopic and microspectrofluorometric investigation with special reference to the innervation of the pituitary.

In the telencephalon and diencephalon of the eel (Anguilla anguilla L.) formaldehyde-induced fluorescence was studied microscopically and microfluorometrically with special emphasis on the innervation of the pituitary. In the telencephalon fluorescent fibers contained predominantly noradrenaline fluorophores. Fluorescent nuclei could not be established. In the diencephalon fluorescent perikarya were found in: (1) the paraventricular organ (PVO), possessing either dopamine or, to a lesser extent, serotonin fluorophores; (2) the PVO-accompanying group, exhibiting spectral data resembling those of noradrenaline fluorophores; (3) the nucleus hypothalami anterior (NHA), a small paired group of catecholamine-containing cells posterior to the commissura transversa.--The nucleus lobi inferioris exhibited a high density of delicate, most probably dopamine-containing terminals, while fibers surrounding this nucleus contained noradrenaline fluorophores. A high density of fluorescent terminals containing dopamine and/or noradrenaline was found in the habenular complex. Fluorescent terminals in the pituitary contained fluorophores resembling either dopamine or noradrenaline. Fluorescent tracts entered the pituitary from different directions. A rostral, unpaired tract enters the neurointermediate lobe, as also verified experimentally. The rostral pars distalis receives two paired tracts, one from a rostral and one from a dorsal direction. The proximal pars distalis also receives two paired tracts, one from a dorsal and one from a posterior direction.

Anguilla↗

Cell migration from the corticostriatal angle to the basal telencephalon in rat embryos.

Lateral cortical stream (LCS) has been described as a flow of cell migration found in the lateral cortex of the embryonic telencephalon of mammals. The destinations of the cell migration were reported as the ventrolateral neocortex, the pyriform cortex, endopyriform nucleus and the claustrum. At the same time, however, other destinations of LCS have been suggested in the ventral telencephalon. Therefore, we investigated the additional destinations of the LCS using a combination of several molecular biological techniques. Using an expression vector of modified green fluorescent protein (GFP) introduced into the ventricular zone (VZ) around the corticostriatal angle, both tangential and radial cell migration was revealed in the LCS. The radial cell migration in the LCS supplied cells to the ventro-lateral neocortex, pyriform cortex and to the level of the lateral olfactory tract. In the second experiment, we injected COS-1 cells transfected with a Sema3A expression vector into one side of the neocortex. The cell supply to the destination of the LCS ceased due to the formation of a large necrosis in the LCS, which was triggered by the Sema3A-COS cell injection, and the dense cell layer in the olfactory tubercle shrunk on the side where COS cells were injected. These data indicated that the majority of neurons in the dense cell layer of the olfactory tubercle reached this point through the LCS. One of the origins of the cells in the LCS would be in the corticostriatal angle.

Animals↗

Expression of L1 and TAG-1 in the corticospinal, callosal, and hippocampal commissural neurons in the developing rat telencephalon as revealed by retrograde and in situ hybridization double labeling.

In the telencephalon, the corticospinal (CS), callosal, and hippocampal commissural neurons are the major types of neurons that have axons crossing the midline of the brain. To understand the mechanisms involved in crossing the midline structure and to examine whether the expression patterns of L1 and TAG-1 in the commissural neurons are similar to those in the spinal cord, we investigated L1 and TAG-1 expression in these neurons in rats by using a double-labeling technique involving retrograde labeling and in situ hybridization. Expression of L1 messenger RNA was detected in the retrogradely labeled CS projection neurons by 1,1;-dioctadecyl-3,3, 3;,3;-tetramethylindocarbocyanine perchlorate (DiI) injection into the pons at embryonic day (E) 19, but expression of TAG-1 messenger RNA was not detected in these neurons. Also, after their axons crossed the pyramidal decussation, continued expression of L1 but no expression of TAG-1 in the CS projection neurons was shown by an additional double-labeling experiment involving DiI injection into the spinal cord at postnatal day (P) 1. An immunohistochemical study showed that L1 was continuously present in each level of the CS tract at E21 and P3, but TAG-1 immunoreactivity was not found in any level at any stage. Finally, we examined the expression of L1 and TAG-1 messenger RNAs in the callosal and hippocampal commissure neurons after their axons had crossed the midline by using the double-labeling technique. In both cases, hybridization signals of the L1 and TAG-1 messenger RNAs were observed in the retrogradely labeled neurons at P3. These results suggest that the roles of L1 and TAG-1 in the formation of the commissures in the forebrain are different from their roles in the spinal cord.

Animals↗

Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1.

Pallial and subpallial morphological subdivisions of the developing chicken telencephalon were examined by means of gene markers, compared with their expression pattern in the mouse. Nested expression domains of the genes Dlx-2 and Nkx-2.1, plus Pax-6-expressing migrated cells, are characteristic for the mouse subpallium. The genes Pax-6, Tbr-1, and Emx-1 are expressed in the pallium. The pallio-subpallial boundary lies at the interface between the Tbr-1 and Dlx-2 expression domains. Differences in the expression topography of Tbr-1 and Emx-1 suggest the existence of a novel "ventral pallium" subdivision, which is an Emx-1-negative pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse belong to the claustroamygdaloid complex. Chicken genes homologous to these mouse genes are expressed in topologically comparable patterns during development. The avian subpallium, called "paleostriatum," shows nested Dlx-2 and Nkx-2.1 domains and migrated Pax-6-positive neurons; the avian pallium expresses Pax-6, Tbr-1, and Emx-1 and also contains a distinct Emx-1-negative ventral pallium, formed by the massive domain confusingly called "neostriatum." These expression patterns extend into the septum and the archistriatum, as they do into the mouse septum and amygdala, suggesting that the concepts of pallium and subpallium can be extended to these areas. The similarity of such molecular profiles in the mouse and chicken pallium and subpallium points to common sets of causal determinants. These may underlie similar histogenetic specification processes and field homologies, including some comparable connectivity patterns.

Age Factors↗

The development of capillaries in the telencephalon of beagle puppies.

The microvessels of the telencephalons of Beagle puppies between newborn and 72 hours of age were investigated ultrastructurally at 24-hour intervals. The morphometry of the microvasculature from the germinal matrix was compared with that of the microvasculature from the borderzone cerebral cortex. The endothelial cell walls of the microvessels from these two sites were similar during the study period, but the lumina of the matrical microvessels were significantly larger than the lumina of the control cortical microvessels. The proportion of matrical microvessels with large lumina undergoes progressive attrition with time. The values (areas) for the lumina of the matrical microvessels, and their distribution, come to resemble those of the cortex. The morphometry of the cortical microvasculature is comparatively static. The data suggest that there is an active modification in the microvasculature of the germinal matrix of the Beagle puppy in the immediate postnatal period.

Animals↗

Cadherin expression coincides with birth dating patterns in patchy compartments of the developing chicken telencephalon.

Some gray matter regions of the vertebrate brain, e.g., the mammalian striatum, are organized into clusters of functionally similar neurons ("patches") that are surrounded by a gray matter matrix. A similar type of compartmentation recently has been found also in the avian telencephalon, based on two sorts of evidence. First, a birth dating study showed that, in some telencephalic areas, cells born at the same time form "isochronic" cell clusters, which differ in their birth dating pattern from their surrounding tissue. Second, patchy expression was found for different members of the cadherin family of adhesion molecules (R-cadherin, N-cadherin, and/or cadherin-7). The relation between these two findings has remained unclear. Here, we demonstrate a general spatial coincidence between the birth dating patterns and the heterogeneities in cadherin expression. This coincidence is found in areas of the avian ventral and lateral pallium (ventral hyperstriatum, neostriatum, and ectostriatum) and in a part of the archistriatum, which is of pallial origin. For example, in the neostriatum, a part of the ventral pallium, both the cadherin-7-positive patches and their R-cadherin-positive surroundings are born between embryonic day 5 and 7, but the cadherin-7-positive cells are born during a shorter time period than the R-cadherin-positive cells. We propose that the patchy gray matter architecture observed in the mammalian striatum and avian pallium are regulated by a common type of morphogenetic mechanism. This mechanism possibly involves the differential expression of adhesive factors, such as cadherins.

Age Factors↗

Retinoic acid signaling in the brain marks formation of optic projections, maturation of the dorsal telencephalon, and function of limbic sites.

As retinoic acid (RA) is known to regulate the expression of many neuronal proteins, it is likely to influence overall development and function of the brain; few particulars, however, are available about its role in neurobiological contexts due mainly to problems in RA detection. To ask whether the function of RA in the rostral brain is concentrated in particular neurobiological systems, we compared sites of RA synthesis and actions, as detected by RA signaling in reporter mice, for embryonic and adult ages. We found that most sites of RA actions in the forebrain do not colocalize with RA synthesis, consistent with a dominant RA supply by diffusion and the circulation. The changing RA patterns distinguish preferentially two complex functional schemes. (1) Within the visual system when the first optic axons grow toward their targets, RA signaling delineates the topographical adjustment of the retinal map, which is encoded in the coordinates of the visual world, to central visual maps, which are formed in the segmental brain coordinates. (2) The second scheme begins early in forebrain morphogenesis as a distinction of the dorsal telencephalon. With progressing development, and in the adult, the RA patterns then focus on widely distributed structures, most of which belong to the limbic system. These are sites in which emotional perception is combined with higher cognitive processes and in which normal function requires ongoing remodeling of synaptic connections, indicating that the developmental role of RA in promotion of neuronal differentiation programs continues in the adult brain for highly flexible neural circuits. J. Comp. Neurol. 470:297-316, 2004.

Animals↗

Expression of the genes Emx1, Tbr1, and Eomes (Tbr2) in the telencephalon of Xenopus laevis confirms the existence of a ventral pallial division in all tetrapods.

To investigate the pallial organization and the exact location and extension of the ventral pallium in amphibians, we cloned a fragment of the homeobox XenopusTbr1 (xTbr1) gene and analyzed its expression compared with that of the genes xEomes (Tbr2) and xEmx1 in the telencephalon of the frog Xenopus laevis during embryonic and larval development. The expression of xEmx1 was also analyzed in the adult frog. We compared the expression patterns of these pallial marker genes with that of the subpallial gene xDistal-less-4 (xDll4). Our results indicate that the whole pallium of Xenopus expresses the T-box genes xTbr1 and xEomes (in proliferating cells and/or mantle) during embryonic and larval development, and the expression of these genes is topographically complementary to that of xDll4 in the subpallium. In addition to their massive expression in the pallium, both xTbr1 and xEomes are expressed in a few dispersed cells in the subpallium, which may represent immigrant cells of pallial origin, because these genes are not found in the subpallial proliferating cells. On the other hand, during development xEmx1 is expressed in a large part of the pallium (proliferating and postmitotic cells) except for an area adjacent to the pallio-subpallial boundary, where xEmx1 is observed only in some mantle cells. This pallial area poor in xEmx1 expression and poor in expression of the subpallial gene xDll4, but expressing the pallial marker genes xTbr1 and xEomes, appears to represent the amphibian ventral pallium, comparable to that described in other vertebrates (Puelles et al. [2000] J. Comp. Neurol. 424:409-438). In the adult frog, the ventral pallium appears to include the rostral part of the lateral amygdalar nucleus as well as a large part of the medial amygdalar nucleus (as defined by Marín et al. [1998] J. Comp. Neurol. 392:285-312). In contrast, the caudal part of the previously termed lateral amygdalar nucleus shows strong xEmx1 expression and may be a lateral pallial derivative. The possible homology of these amphibian amygdalar nuclei is discussed. Finally, expression of xTbr1, xEomes, and xEmx1 is observed in the mitral cell layer of the olfactory bulb from early developmental stages, further supporting that this structure is a pallial derivative.

Animals↗

Connectivity and cytoarchitecture of the ventral telencephalon in the salamander Plethodon shermani.

The cytoarchitecture and axonal connection pattern of centers in the ventral telencephalon of the salamander Plethodon shermani were studied using biocytin for anterograde and retrograde labeling of cell groups, as well as by intracellular injections. Application of biocytin to the main and accessory olfactory bulbs identified the olfactory pallial regions and the vomeronasal portion of the amygdala, respectively. According to our results, the amygdala of Plethodon is divided into (1) a rostral part projecting to visceral and limbic centers and receiving afferents from the dorsal thalamus, and (2) a caudal part receiving accessory olfactory input. The striatopallial transition area (SPTA) lies rostrodorsally to the caudal (vomeronasal) amygdala and is similar in connections and possibly in function. The rostral striatum has few descending projections to the medulla, whereas the intermediate striatum sends strong projections to the tegmentum and medulla. The caudal striatum has strong ascending projections to the striatum and descending projections to the ventral hypothalamus. The dendritic trees of neurons labeled below the striatum and in the SPTA spread laterally from the soma, whereas dendrites of striatal neurons converge into the laterally situated striatal neuropil. In the caudal amygdala, three distinct types of neurons are found differing in dendritic arborization. It is concluded that, hodologically, the rostral part of the urodele amygdala corresponds to the central and basolateral amygdala and the caudal part to the cortical/medial amygdala of mammals. The urodele striatum is divided into a rostral striatum proper, an intermediate dorsal pallidum, and a caudal part, with distinct connections described here for the first time in a vertebrate.

Animals↗

Region- and age-specific deficits in gamma-aminobutyric acidergic neuron development in the telencephalon of the uPAR(-/-) mouse.

We have previously shown that in adult mice with a null mutation in the urokinase-type plasminogen activator receptor (uPAR) gene, maintained on a C57BL/6J/129Sv background, there is a selective loss of GABAergic interneurons in anterior cingulate and parietal cortex, with the parvalbumin-expressing subpopulation preferentially affected. Here, we performed a more detailed anatomical analysis of uPAR(-/-) mutation on the congenic C57BL/6J background. With glutamic acid decarboxylase-67 and gamma-aminobutyric acid (GABA) immunostaining, there is a similar region-selective loss of cortical interneurons in the congenic uPAR(-/-) mice from the earliest age examined (P21). In contrast, the loss of parvalbumin-immunoreactive cells is observed only in adult cortex, and the extent of this loss is less than in the mixed background. Moreover, earlier in development, although there are normal numbers of parvalbumin cells in the uPAR(-/-) cortex, fewer cells coexpress GABA, suggesting that the parvalbumin subpopulation migrates appropriately to the cortex, but does not differentiate normally. Among the other forebrain regions examined, only the adult hippocampus shows a loss of GABAergic interneurons, although the somatostatin, rather than the parvalbumin, subpopulation contributes to this loss. The data suggest that uPAR function is necessary for the normal development of a subpopulation of GABAergic neurons in the telencephalon. It is likely that the late-onset parvalbumin phenotype is due to the effects of an altered local environment on selectively vulnerable neurons and that the extent of this loss is strain dependent. Thus, an interplay between complex genetic factors and the environment may influence the phenotypic impact of the uPAR mutation both pre- and postnatally.

Aging↗

Topography and connections of the telencephalon in a chondrostean, Acipenser baeri: an experimental study.

Sturgeons belong to an ancient group of the extant actinopterygian fishes. Accordingly, the study of their brain connections is important to understand brain evolution in the line leading to teleosts. We examined the topography and connections of the various telencephalic regions of the Siberian sturgeon (Acipenser baeri). The telencephalic regions were characterized on the basis of acetylcholinesterase histochemistry and calbindin-D28k and calretinin immunohistochemistry. The telencephalic connections were investigated by using the fluorescent dye DiI (1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate) in fixed brains. Application of DiI to different areas of the pallial (dorsal) regions of the telencephalic lobes showed that they have mostly intratelencephalic connections. A posterior pallial region is characterized by its similar hodology to that of the posterior zone of the teleosts dorsal telencephalon and those described in other ancient groups. Extratelencephalic connections of the pallium are scarce, although a few afferent and efferent connections with the diencephalon, mesencephalon, and rostral rhombencephalon were observed. DiI application to subpallial regions showed both intratelencephalic connections and connections with different brain regions. Afferents to the subpallium originate from the olfactory bulbs, preoptic area, thalamus, posterior tuberculum, hypothalamus, secondary gustatory nucleus, and raphe nuclei. Some of these connections are quite similar to those described for other vertebrates.

Acetylcholine↗

Ascending afferents to the telencephalon of ranid frogs: an anterograde degeneration study.

Sources of telencephalic afferents were examined in two species of frogs, Rana catesbeiana and Rana pipiens, by study of anterograde degeneration resulting from hemisection of the brain at the isthmus or at the caudal border of the thalamus and from electrolytic lesions in various portions of the diencephalon. The results indicate that some telencephalic afferents arise from levels caudal to the isthmus, that some striatal afferents arise from a level between the isthmus and the caudal border of the thalamus, and that a projection to the ipsilateral striatum arises from the anterior and/or middle portions of the dorsal thalamus. Diencephalic projections to pallial portions of the hemisphere were also observed. These results demonstrate substantial non-olfactory afferent projections to the telencephalon in ranid frogs.

Animals↗