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At least 19 recordsLinked to original sources
PubMed1997

Early development of the oligodendrocyte in the embryonic chick metencephalon.

It has been demonstrated that the spinal cord oligodendrocytes in the vertebrates arise in the ventral ventricular zone adjacent to the floor plate in their early development. Because of the similarities of basic structures in the spinal cord and metencephalon, it is probable that the mode of early oligodendrocyte development in the metencephalon is the same as that in the spinal cord. We examined this possibility in chick embryos, using monoclonal antibodies O1 and O4, markers for oligodendrocyte lineage. An O4-positive (O4+) cell focus was observed in the medial ventricular zone of E5 chick ventral metencephalon (the earliest stage examined), adjacent to the floor plate. At E6, O4+ cells were dispersed from the medial to the lateral pons and, at E7, to the cerebellar anlagen. O4+ cells in the E6 brainstem and in the E7 cerebellum were unipolar in shape, whereas one day later, some of the labeled cells were multipolar with a few thin processes. O1+ oligodendrocytes first appeared at E8 in the ventromedial part of the pons and were distributed throughout the pons at E10 and in the cerebellum at E12. Explants from three subdivisions of the metencephalon (medial and lateral pons, and cerebellum) from E5 to E8 chick embryos were separately cultured to confirm the potential for generation of oligodendrocyte lineage. O4+ cells appeared in the culture of the E5 medial pons (the earliest stage examined), in the E6 lateral pons, and in the E7 cerebellum. In addition, E7 was the youngest stage from which cerebellar explants were able to generate O1+ oligodendrocytes. Our results clearly demonstrated the in vivo morphology of oligodendrocyte precursors in the metencephalon and their developmental appearance in a ventral-to-dorsal manner. From the bipolar morphology of O4+ cells and the spacio-temporal continuity of the dispersion, it is inferred that the initial dispersion of O4+ cells may involve oligodendrocyte migration from the focus of the medial pons to the lateral and dorsal parts of the metencephalon.

Animals↗
PubMed2001

Local sonic hedgehog signaling regulates oligodendrocyte precursor appearance in multiple ventricular zone domains in the chick metencephalon.

In the chick metencephalon, oligodendrocyte precursors arise in distinct domains of the ventricular zone. During development, the earliest oligodendrocyte precursors appear in the metencephalic ventral ventricular zone adjacent to the midline, consistent with their location in the spinal cord. In contrast to spinal cord, however, distinct domains in the lateral and dorsal metencephalic ventricular zone subsequently generate oligodendrocyte precursors. All oligodendrogenic domains of the metencephalon appear in close apposition to regions that transiently express sonic hedgehog (Shh). Inhibition studies demonstrate a functional requirement for Shh signaling in the early appearance of metencephalic oligodendrocyte precursors, while in vitro studies suggest a dose-dependent increase in the number of oligodendrocyte precursors in response to Shh. In purified cultures of oligodendrocyte precursors, Shh promotes cell survival and proliferation, suggesting that Shh can act directly on these cells. These data suggest that Shh may be responsible for the localized appearance of oligodendrocyte precursors throughout the CNS, irrespective of the dorso-ventral neural axis.

Animals↗
PubMedDate not supplied

Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene--report of 2 cases in early infancy.

Congenital absence of the midbrain and upper pons is a rare human malformation. We describe two unrelated infants with this anomaly and cerebellar hypoplasia who were born at term but died in early infancy from lack of central respiratory drive. MRI in both cases disclosed the lesions during life. Neuropathological examination, performed in one, included immunocytochemical studies of NeuN, synaptophysin, vimentin, and glial fibrillary acidic protein (GFAP). Autopsy revealed a thin midline cord passing through the clivus, in place of the midbrain; it corresponded to hypoplastic and fused corticospinal tracts with ectopic neural tissue in the surrounding leptomeninges. Some ectopia were immunoreactive for synaptophysin and NeuN and others were nonreactive. The neural surfaces facing the subarachnoid fluid-filled space left by the absent midbrain and upper pons were lined by an abnormal villous ependyma. The architecture of the cerebellar cortex was imperfect but generally normal, and Bergmann glial cells had normal radial processes shown by vimentin and GFAP. Structures of the telencephalon, diencephalon, lower brainstem, and spinal cord were generally well formed, but inferior olivary and dentate nuclei were rudimentary and the spinal central canal was dilated at lumbar levels. The cerebral cortex was normally laminated, but pyramidal neurons of layer 5 were sparse in the frontal lobes. The hippocampus, olfactory system, and corpus callosum were formed. An ectopic lingual thyroid was found and had been associated with hypothyroidism during life. A murine model resembling this dysgenesis is demonstrated by homozygous mutations of the organizer genes Wnt1 or En1, also resulting in cerebellar aplasia, and En2, associated with cerebellar hypoplasia. These genes are essential to the formation of the mesencephalic neuromere and rhombomere 1 (metencephalon or upper pons and cerebellum). Pax8 has binding sites in the promoter for En2 and is essential for thyroid development. We speculate that in the human, the failure to form a mesencephalon and metencephalon, with cerebellar hypoplasia, results from a mutation or deletion in the EN2 (Engrailed-2) gene.

Brain↗
PubMed1981

Chemoarchitectonics of metencephalon of Testudo elegant.

Histoenzymological study of acid phosphatase (GP-AI), 5-nucleotidase (AMP-A), adenosine triphosphatase (ATP-A) and beta-galactosidase (GLAC-A) of the metencephalon of turtle shows a pattern of distribution of enzymes similar to amphibians and mammalian metencephalon which provides indication of homology of the nuclei and tracts such as nucleus raphe, nuclei cerebelli fasciculus longitudinalis medialis, commissura ansulata and internal arcuate fibers. The nerve fibers, tracts and commissures demonstrate strong activity of GLAC-A as demonstrated in frog and bat by the author in previous studies.

Acid Phosphatase↗
PubMed2005

Isthmus organizer and regionalization of the mesencephalon and metencephalon.

The brain vesicles that are formed at an early stage of neural development are the fundamentals of the brain plan. Heterotopic transplantation revealed that the diencephalon could change its fate when juxtaposed to the isthmus (mes-metencephalic boundary), which indicated that the isthmus functions as an organizer for the mesencephalon and metencephalon. Fgf8 is identified as an isthmus organizing signal. Misexpression of Fgf8a and Fgf8b indicated that a strong Fgf8 signal organizes cerebellar development. The transcription factors define the fate of the region. Overlapping expression of Otx2, En1 and Pax2 may define the mesencephalic region and additional expression of Pax3/7 may instruct the mesencephalic region to differentiate into the tectum. The di-mesencephalic boundary is determined by repressive interaction between Pax6 and En1/Pax2 and the mes-metencephalic boundary is defined by repressive interaction between Otx2 and Gbx2. Fgf8 is induced at the border of the Otx2 and Gbx2 expression domain, overlapping with Gbx2 expression.

Animals↗
PubMed1991

Primary dissociated cell culture of embryonic rat metencephalon: presence of GABA in serotonergic neurons.

This study was performed to determine whether neurons, where gamma-aminobutyric acid (GABA) and serotonin (5-HT) coexist, represent neuronal entities which can survive in vitro. In dissociated cultures from 18-day-old embryonic rat metencephalon, it was possible to develop glial and neuronal cells. Among the neurons, some of them, which contain glutamate decarboxylase or are capable of accumulating [3H]GABA are GABAergic; others, containing tryptophan hydroxylase or 5-HT are serotoninergic. By combining radioautography and immunocytochemistry, it was possible to observe neurons where 5-HT and GABA coexist. Cultures might be a suitable model to study the functioning (release or synthesis of both neurotransmitters) of neurons where two classical neurotransmitters coexist.

Animals↗
PubMed1986

[Catecholaminergic nuclei of sheep encephalon. Immunocytochemical study. I. Myelencephalon and metencephalon].

Using an anti-tyrosine hydroxylase antiserum, the whole of catecholaminergic perikarya of the myelencephalon and metencephalon of the sheep were visualized immunocytochemically. Compared with those of the rat, these neuronal groups in the sheep were featured, firstly, by a greater dispersion relative to their perikarya and, secondly, by the absence of A3 and A4 nuclei described by Dahlstrom and Fuxe.

Animals↗
PubMed2002

Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development.

The isthmus is the organizing center for the tectum and cerebellum. Fgf8 and Wnt1 are secreted molecules expressed around the isthmus. The function of Fgf8 has been well analyzed, and now accepted as the most important organizing signal. Involvement of Wnt1 in the isthmic organizing activity was suggested by analysis of Wnt1 knockout mice. But its role in isthmic organizing activity is still obscure. Recently, it has been shown that Lmx1b is expressed in the isthmic region and that it may occupy higher hierarchical position in the gene expression cascade in the isthmus. We have carried out misexpression experiment of Lmx1b and Wnt1, and considered their role in the isthmic organizing activity. Lmx1b or Wnt1 misexpression caused expansion of the tectum and cerebellum. Fgf8 was repressed in a cells that misexpress Lmx1b, but Fgf8 expression was induced around Lmx1b-misexpressing cells. As Lmx1b induced Wnt1 and Wnt1 induced Fgf8 expression in turn, Wnt1 may be involved in non cell-autonomous induction of Fgf8 expression by Lmx1b. Wnt1 could not induce Lmx1b expression so that Lmx1b may be put at the higher hierarchical position than Wnt1 in gene expression cascade in the isthmus. We have examined the relationship among isthmus related genes, and discuss the mechanism of the formation and maintenance of isthmic organizing activity.

Animals↗
PubMed1975

[Histochemical evidence of aminotransferases. II. Localization of aminotransferases in the medulla spinalis and metencephalon of the rat (author's transl)].

The cytochemical and topochemical localization of 10 aminotransferases have been studied in a serial slices through the spinal cord, medulla oblongata, pons and cerebellum of the rat. In the gray matter a high enzyme activity was observed. The reaction product was localized in the cells and the surrounding neuropil. The cell nuclei were found negativ. In some nuclei aminotransferase activity was higher in the neurons than in the neuropil. In the other nuclei there were no recognizable differences in staining intensity between the neurons and the neuropil. The nerve cells of spinal cord and reticular formation, nuclei n. hypoglossi and n. facialis, nucl. vestibularis lateralis and the Purkinje cells exhibited particularly high aminotransferase activity.

Alanine Transaminase↗
PubMed1989

[Demonstration of direct olfactory projections in the hypothalamus, the mesencephalon and the metencephalon of Microcebus murinus (Primate, Lemurian)].

The efferent projections of the olfactory bulb in Microcebus murinus were identified after transection of the olfactory peduncle and after the revelation of the degenerating fibers by different silver staining methods. Total and partial sections have allowed demonstrating the importance of the two olfactory tracts in the olfactory projection areas. Degenerated fibers and endings were evidence not only in the different telencephalic regions, as classically known, but also in various hypothalamic nuclei (lateral hypothalamus, the suprachiasmatic, posterior supraoptic and mammillary nuclei and in the median eminence) and in several mesencephalic and metencephalic nuclei (ventral tegmental area, interpeduncular and raphe nuclei, and locus coeruleus). In all these structures the degenerate fibers were seen on both sides. The olfactory projections appeared not to be limited to the telencephalic areas. Moreover, the olfactory bulbs seem to be directly connected especially with the vegetative and integrative areas localized in the hypothalamus and the brainstem and particularly with the major aminergic nuclei that play an essential role in the neurovegetative, neuroendocrine and behavioral regulations.

Animals↗
PubMedDate not supplied

[Developmental anomalies of the metencephalon in the craniofacial and vertebral malformation syndrome].

The authors describe a case of a girl aged 9 years with a syndrome of malformations--cleft of the upper lip, maxilla and palate, lack of C2 arch fusion, polycystic lesions of the vermis and cerebellar hemisphere with obliteration of the aqueduct. The syndrome of intracranial hypertension with prevailing cerebellar symptoms was the cause of diagnostic and surgical management. Suboccipital craniotomy was done with insertion of ventriculoatrial valve which restored the normal intracranial pressure. The girl recovered and resumed education.

Abnormalities, Multiple↗
PubMed1996

Cell death in the CNS of the Wnt-1 mutant mouse.

Using the benzothiazolium-4-quinolium dye, TO-PRO-1, to detect cell death in live embryos, we labeled a developmental series of Wnt-1 null mutant and wild type embryos to determine if cell death contributed to the absence of the midbrain and rostral metencephalon observed in Wnt-1 mutant embryos. We found that there is no detectable cell death at early somite stages in Wnt-1 mutant embryos. However, we detected a significant, but transient, population of dying cells within the anterior dorsal metencephalon in 20-29 somite stage embryos. These cells located in the anterior dorsal metencephalon also stain positive using the TUNEL technique that utilizes terminal transferase to label DNA fragments that are typical in the nuclei of apoptotic cells. Thus, programmed cell death plays a role in the loss of the metencephalon, but apparently does not contribute to the earliest aspect of the mutant phenotype, namely the loss of the midbrain.

Animals↗
PubMed1990

Pluripotentiality of the 2-day-old avian germinative neuroepithelium.

In a previous study using chick/quail chimeric embryos with homotopic transplants (Martinez & Alvarado-Mallart, 1989b), we have delimited in the 2-day-old avian embryo the areas of the neural tube giving rise to optic tectum and mesencephalic grissea as well as to isthmic grissea and cerebellum: respectively, "mesencephalic" and "metencephalic" alar plates. To investigate the determination or the competence of these areas, portions of these germinative neuroepithelia from a quail embryo were transplanted in substitution for other areas of the chick neural tube. The analysis of the chimeric brains was done by comparing alternating transverse sections stained for cytoarchitecture and with two different techniques to recognize transplanted versus host cells: either the Feulgen and Rossenbeck DNA histochemical reaction and/or immunohistochemical methods with a monoclonal antibody recognizing quail but not chick cells. The eventual visual innervation of the quail graft was analyzed in many cases by injecting anterograde axonal tracers in the eye contralateral to the graft. The results are as follows: (1) caudal metencephalon transferred to mesencephalon maintained in all cases its presumptive cerebellar phenotype, whereas (2) rostral metencephalon transferred to mesencephalon changed its fate to a tectal phenotype but maintained its cerebellar fate when transferred to diencephalon; (3) caudal mesencephalon maintained its tectal fate in 65% of the cases when transferred to diencephalon, whereas (4) rostral mesencephalon transferred to a cerebellar domain changed its fate and became influenced by the surrounding structures in all cases, but only in 85% of the cases when it was transplanted to diencephalon; (5) the in situ host diencephalon, isolated from its normal environment by a mesencephalic graft, is competent to change its fate and express a mesencephalic phenotype. These results demonstrate that at least some regions of the germinative neuroepithelium from either metencephalon, mesencephalon, and diencephalon are still pluripotent in the 2-day-old avian embryo and that their fate seems to be under the influence of the surrounding structures. Rostral mesencephalon and rostral metencephalon have been more easily influenced by environmental factors than their caudal counterparts, suggesting that regions providing instructive positional factors exist within the 2-day-old germinative neuroepithelium. These regions might play an important role in the determination of the various segments of the neural tube.

Animals↗
PubMed1983

Developmental relationships between trigeminal ganglia and trigeminal motoneurons in chick embryos. II. Ganglion axon ingrowth guides motoneuron migration.

In the chick embryo the trigeminal (V) sensory ganglion cells send axons into the metencephalon a few hours before the V motoneurons migrate from the midline to form a lateral nucleus adjacent to the ingrowing sensory axons. This relationship suggests that the ganglion axons may influence the initiation and direction of V motoneuron migration. In the present experiment the development of the ganglion axons was retarded by removing the neural crest anlage of the V ganglion. Subsequently, V ganglion cells which were derived from the ectodermal placode anlage sent axons into the metencephalon up to 2 days later than normal. The lateral migration of the V motoneurons was similarly delayed, commencing only after the central axons from the placodal ganglia penetrated the metencephalon. This study demonstrates that the presence of V ganglion perikarya alone is not sufficient to guide the appropriate migration of V motoneurons. This migration occurs only after the axons from the V sensory ganglion cells have penetrated the brainstem.

Animals↗
PubMed1997

Spatially and temporally regulated modification of the receptor-like protein tyrosine phosphatase zeta/beta isoforms with keratan sulphate in the developing chick brain.

Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. In addition to the transmembrane form (PTPzeta-A), the extracellular splice variant (PTPzeta-S) occurs as a major soluble chondroitin sulphate proteoglycan in the brain. We prepared antibodies which specifically recognize PTPzeta-A and -S, and analysed the carbohydrate structures on the two PTPzeta isoforms in the developing chick brain. Immunoprecipitation experiments using these antibodies revealed that almost all of the keratan sulphate recognized by a monoclonal antibody (5D4) was exclusively bound to PTPzeta-A and PTPzeta-S. Addition of keratan sulphate to these proteoglycans markedly increased from embryonic day (E) 11, in contrast to the addition of Le(x) and HNK-1 carbohydrates, which gradually increased during development in accordance with expression of the core proteins, suggesting that keratan sulphate modification plays some specific roles. Moreover, at the early embryonic stage keratan sulphate was observed only in several restricted regions, especially at boundary regions such as the roof plate of the tectum, the zona limitans intrathalamica in the diencephalon, and the mesencephalon-metencephalon boundary. At the mesencephalon-metencephalon boundary, keratan sulphate modification of PTPzeta isoforms was specifically observed from E3 to E6 on a ring of cells encircling the neural tube and their radially oriented processes, which were identified as radial glial fibres. This expression pattern of keratan sulphate spatiotemporally corresponded well to the formation of the fovea isthmi, a groove separating the mesencephalon from the metencephalon. These results suggest that carbohydrates including keratan sulphate on PTPzeta isoforms play important roles in brain development by modulating the cell-cell and/or cell-substrate interactions mediated by these molecules.

Animals↗
PubMed1997

Genetic control of brain morphogenesis through Otx gene dosage requirement.

Understanding the genetic mechanisms that control patterning of the vertebrate brain represents a major challenge for developmental neurobiology. Previous data suggest that Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, might both contribute to brain morphogenesis. To gain insight into this possibility, the level of OTX proteins was modified by altering in vivo the Otx gene dosage. Here we report that Otx genes may cooperate in brain morphogenesis and that a minimal level of OTX proteins, corresponding either to one copy each of Otx1 and Otx2, or to only two copies of Otx2, is required for proper regionalization and subsequent patterning of the developing brain. Thus, as revealed by anatomical and molecular analyses, only Otx1-/-; Otx2+/- embryos lacked mesencephalon, pretectal area, dorsal thalamus and showed an heavy reduction of the Ammon's horn, while the metencephalon was dramatically enlarged occupying the mesencencephalic area. In 8.5 days post coitum (d.p.c.) Otx1-/-; Otx2+/- embryos, the expression patterns of mesencephalic-metencephalic (mes-met) markers such as En-1 and Wnt-1 confirmed the early presence of the area fated to give rise to mesencephalon and metencephalon while Fgf-8 transcripts were improperly localized in a broader domain. Thus, in Otx1-/-; Otx2+/- embryos, Fgf-8 misexpression is likely to be the consequence of a reduced level of specification between mes-met primitive neuroepithelia that triggers the following repatterning involving the transformation of mesencephalon into metencephalon, the establishment of an isthmic-like structure in the caudal diencephalon and, by 12.5 d.p.c., the telencephalic expression of Wnt-1 and En-2. Taken together these findings support the existence of a molecular mechanism depending on a precise threshold of OTX proteins that is required to specify early regional diversity between adjacent mes-met territories and, in turn, to allow the correct positioning of the isthmic organizer.

Animals↗
PubMed2001

Crossing the floor plate triggers sharp turning of commissural axons.

During development of the vertebrate CNS, commissural axons initially grow circumferentially toward the ventral midline floor plate. After crossing the floor plate, they abruptly change their trajectory from the circumferential to the longitudinal axis. Although recent studies have unraveled the mechanisms that control navigation of these axons along the circumferential axis, those that result in the transition from circumferential to longitudinal trajectory remain unknown. Here, we examined whether an interaction with the floor plate is a prerequisite for the initiation of trajectory transition of commissural axons, using in vitro preparations of the rat metencephalon. We found that commissural axons in the metencephalon, once having crossed the floor plate, turned sharply to grow longitudinally. In contrast, axons extending in floor plate-deleted preparations, continued to grow circumferentially, ignoring the hypothetical turning point. These results suggest that a prior interaction of commissural axons with floor plate cells is a key step for these axons to activate a navigation program required for their change in axonal trajectory from the circumferential to the longitudinal axis.

Animals↗