Pax gene expression in the developing central nervous system of Ciona intestinalis

We compare the expression patterns in Ciona intestinalis of three members of the Pax gene family, CiPax3/7, CiPax6 and Cipax2/5/8. All three genes are expressed in restricted patterns in the developing central nervous system. At the tailbud stage, CiPax3/7 is present in three patches in the brain and along the posterior neural tube, CiPax6 throughout the anterior brain and along the posterior neural tube and CiPax2/5/8 in a restricted region of the posterior brain. Double in situ hybridisations were used to identify areas of overlap between the expression of different genes. This showed that CiPax3/7 overlaps with the boundaries of CiPax6 expression in the anterior brain, and with CiPax2/5/8 in the posterior brain. The overlap between CiPax3/7 and CiPax2/5/8 is unlike that described in the ascidian Halocynthia rorezti.     

Glial cells phagocytose neuronal debris during the metamorphosis of the central nervous system in Drosophila melanogaster

 Using electron microscopy we demonstrate that degenerating neurons and cellular debris resulting from neuronal reorganization are phagocytosed by glial cells in the brain and nerve cord of the fruitfly Drosophila melanogaster during the first few hours following pupariation. At this stage several classes of glial cells appear to be engaged in intense phagocytosis. In the cell body rind, neuronal cell bodies are engulfed and phagocytosed by the same glial cells that enwrap healthy neurons in this region. In the neuropil, cellular debris in tracts and synaptic centres resulting from metamorphic re-differentiation of larval neurons is phagocytosed by neuropil-associated glial cells. Phagocytic glial cells are hypertrophied, produce large amounts of lysosome-like bodies and contain a large number of mitochondria, condensed chromatin bodies, membranes and other remains from neuronal degeneration in phagosomes. Received: 23 January 1996 / Accepted in revised form: 21 May 1996     

神经系统内高亲和谷氨酸摄取及其调节影响因素

神经系统内高亲和谷氨酸１（Ｇｌｕ）摄取是Ｎａ＾＋依赖性的,由Ｇｌｕ能神经末梢及胶质细胞膜上的Ｇｌｕ转运蛋白介导。已克隆得到四种Ｇｌｕ转运蛋白,分别为ＧＬＡＳＴ１、ＧＬＵＴ１、ＥＡＡＣ１及ＥＡＡＴ４。它们的所在部位、分布及药理学性质都有自己的特点。花生四烯酸、一氧化氮、氧自由基、蛋白激酶、细胞因子及生长因子等多种因素能调节或影响高亲和Ｇｌｕ摄取。很显然这些因素的调节或影响效应具有一定生理及病理生理意     

ErbB receptors and the development of the nervous system

Tyrosine kinase receptors and their ligands allow communication between cells in the developing and adult organism. An extensive line of research has revealed that ‘neuregulins’, a family of EGF-like factors that signal via ErbB receptors, are used frequently for cell communication during nervous system development, and control a spectacular spectrum of developmental processes. For instance, during development of the peripheral nervous system, Schwann cells require neuronally-produced neuregulin (Nrg1) for growth, migration and myelination, neural crest cells rely on mesenchymally-generated Nrg1 signals for migration, while muscle requires neuronally-produced Nrg1 for the differentiation of a muscle spindle. In the central nervous system, neuregulin signals allow cells to act as guideposts or as barriers for axons during pathfinding. Neuregulin signals are also important in other organs, but the nervous system functions have received recently considerable attention due to the finding that particular haplotypes of Nrg1 and ErbB4 predispose to schizophrenia. Understanding the neuregulin signaling system can thus contribute to define causes of this devastating mental disorder.     

Photosensitization and the nervous system in the planarian Dugesia gonocephala

Summary Photosensitization phenomena may be induced in planarias by eosin and hematoporphyrin, and as a result, dopamine agonistic behavior (screw-like hyperkinesia) is set up in the animal. Histochemical, ultrastructural and pharmacological investigations have shown that this hyperkinesia is of postsynaptic origin in eosin photosensitization, and of pre-synaptic origin in hematoporphyrin photosensitization. The authors suggest an hypothesis to explain the different activity of the two photosensitizers, and discuss the validity of the experiment with regard to human porphyria.     

Fine structure of a lepidopteran nervous system and its accessibility to peroxidase and lanthanum

Summary The avascular ventral nerve cord of the moth, Manduca sexta, possesses an extensive dorsal mass of connective tissue in which lie fibroblasts that produce a collagen-like protein. The lateral and ventral surfaces of the nerve cord are ensheathed by an acellular neural lamella. Beneath this lies a layer of microtubule-laden perineurial cells which are separated from one another at their peripheral borders by lacunae containing electron-opaque material to which the cells are attached by hemi-desmosomes. Beyond these spaces, narrow intercellular clefts occur between the interdigitating perineurial plasma membranes; these are then connected by both gap and tight junctions. The axons beneath are surrounded by glia which also contain many microtubules and which are linked to one another by desmosomes and tight junctions.When intact nerve cords are incubated in horseradish peroxidase, reaction product is subsequently found within the neural lamella as well as in the lacunae and clefts between perineurial cells, but not beyond this level. Desheathed preparations, however, contain peroxidase within the cytoplasm of the exposed glial cells. Lanthanum penetrates the neural lamella and the lacunae, clefts and gap junctions between adjacent perineurial cells, but no further. It therefore appears that the tight junctions in the perineurium may be the site of restriction to the entry of ions and molecules, the existence of which has been suggested previously by electrophysiological investigations.I am grateful to Miss Yvonne R. Carter for her invaluable technical assistance and to Dr. J.E. Treherne and Dr. D.B. Sattelle for helpful discussions.     

Chromosome-level organization of the regulatory genome in the Drosophila nervous system

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Development of the rhopalial nervous system in <Emphasis Type="Italic">Aurelia</Emphasis> sp.1 (Cnidaria,Scyphozoa)

We examined the development of the nervous system in the rhopalium, a medusa-specific sensory structure, in Aurelia sp.1 (Cnidaria, Scyphozoa) using confocal microscopy. The rhopalial nervous system appears primarily ectodermal and contains neurons immunoreactive to antibodies against tyrosinated tubulin, taurine, GLWamide, and FMRFamide. The rhopalial nervous system develops in an ordered manner: the presumptive gravity-sensing organ, consisting of the lithocyst and the touch plate, differentiates first; the “marginal center,” which controls swimming activity, second; and finally, the ocelli, the presumptive photoreceptors. At least seven bilaterally arranged neuronal clusters consisting of sensory and ganglion cells and their neuronal processes became evident in the rhopalium during metamorphosis to the medusa stage. Our analysis provides an anatomical framework for future gene expression and experimental studies of development and functions of scyphozoan rhopalia. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

The fine structure of neuroglia in the central nervous system of nereid polychaetes

Summary The principal supportive elements of the nereid central nervous system are non-neuronal cells that are referred to as supportive glia. Supportive glial cells form a conspicuous cortex in the nerve cord. The inner region of this cortex consists of closely packed processes and cell bodies of fibrous supportive glial cells that are arranged in concentric layers around the perimeter of the neuropile. The fibrous appearance of the glial cells results from dense bundles of cytoplasmic filaments. Many fibrous glial processes penetrate the neuropile and ramify among the neuronal elements. Larger, irregularly shaped cells are the chief supportive glial elements of the peripheral region of the cortex where they line the stromal sheath (neural lamella) and invest the neuronal perikarya with extensive concentric systems of lamellate processes. These glial cells usually possess a relatively undifferentiated cytoplasm with scattered glycogen granules, but occasionally have a well developed Golgi apparatus, endoplasmic reticulum and densely packed particulate glycogen. The supportive glia exhibits numerous desmosomes as well as 5-layered (tight) and 7-layered (gap) junctions. Interspersed among the supportive glial cells are non-neuronal cells referred to as granulocytes. These cells have abundant large, granular inclusions, electron lucent vesicles, plasmalemmal infoldings and microtubules. The granulocytes may be derived from undifferentiated glial cells or may represent coelomocytes that have invaded the nervous tissue.Supported by USPHS Grants No. NIH 5P01 NS-07512, NIH 2T01 GM-00102, and NB-00840.The author acknowledges the excellent technical assistance of Sarah Wurzelmann and Stanley Brown, and thanks Dr. Berta Scharrer for many stimulating discussions.     

Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system

The developing central nervous system is partitioned into compartments by boundary cells, which have different properties than compartment cells, such as forming neuron-free zones, proliferating more slowly and acting as organizing centers. We now report that in mice the bHLH factor Hes1 is persistently expressed at high levels by boundary cells but at variable levels by non-boundary cells. Expression levels of Hes1 display an inverse correlation to those of the proneural bHLH factor Mash1, suggesting that downregulation of Hes1 leads to upregulation of Mash1 in non-boundary regions, whereas persistent and high Hes1 expression constitutively represses Mash1 in boundary regions. In agreement with this notion, in the absence of Hes1 and its related genes Hes3 and Hes5, proneural bHLH genes are ectopically expressed in boundaries, resulting in ectopic neurogenesis and disruption of the organizing centers. Conversely, persistent Hes1 expression in neural progenitors prepared from compartment regions blocks neurogenesis and reduces cell proliferation rates. These results indicate that the mode of Hes1 expression is different between boundary and non-boundary cells, and that persistent and high levels of Hes1 expression constitutively repress proneural bHLH gene expression and reduce cell proliferation rates, thereby forming boundaries that act as the organizing centers.     

The relationship between excitotoxicity and oxidative stress in the central nervous system

Excitotoxicity and oxidative stress are two phenomena that have been repeatedly described as being implicated in a wide range of disorders of the nervous system. Such disorders include several common idiopathic neurological diseases, traumatic brain injury, and the consequences of exposure to certain neurotoxic agents. While there is evidence that metabolic derangements can laed to these adverse processes, and that these processes may synergize in their damaging effects, the degree of interdependence, and the causal relation between them is not clear. The intent of this review is to delineate potential mechanisms which may unit hyperexcitation to the excessive generation of reactive oxygen species. The degree of linkage between these events appears rather strong. It is likely that excitoxicity frequency leads to a pro-oxidant condition but that high rates of generation of reactive oxygen species are not invariably accompanied by a hyperexcited neuronal state Both excitoxic and ‘oxidotoxic’ states result from the failure of normal compensatory anti excitatory and antioxidant mechanisms to maintain cellular homeostatis.     

Development and sensitivity to serotonin of Drosophila serotonergic varicosities in the central nervous system

Serotonin is a classical small-molecule neurotransmitter with known effects on developmental processes. Previous studies have shown a developmental role for serotonin in the fly peripheral nervous system. In this study, we show that serotonin can modulate the development of serotonergic varicosities within the fly central nervous system. We have developed a system to examine the development of serotonergic varicosities in the larval CNS. We use this method to describe the normal serotonergic development in the A7 abdominal ganglion. From first to third instar larvae, the volume of the neuropil and number of serotonergic varicosities increase substantially while the varicosity density remains relatively constant. We hypothesize that serotonin is an autoregulator for serotonergic varicosity density. We tested the sensitivity of serotonergic varicosities to serotonin by adding neurotransmitter at various stages to isolated larval ventral nerve cords. Addition of excess exogenous serotonin decreases native varicosity density in older larvae, and these acute effects are reversible. The effects of serotonin appear to be selective for serotonergic varicosities, as dopaminergic and corazonergic varicosities remain qualitatively intact following serotonin application.     

The distribution of NADPH diaphorase activity and immunoreactivity to nitric oxide synthase in the nervous system of the pulmonate mollusc Helix aspersa

Enzyme histochemistry and immunocytochemistry were used to determine the distribution of neurons in the snail Helix aspersa which exhibited nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and/or immunoreactivity to nitric oxide synthase (NOS). NADPH diaphorase-positive cells and fibres were distributed extensively throughout the central and peripheral nervous system. NADPH diaphorase-positive fibres were present in all neuropil regions of the central and peripheral ganglia, in the major interganglionic connectives and in peripheral nerve roots. NADPH diaphorase-positive cell bodies were found consistently in the eyes, the lips, the tentacular ganglia and the procerebral lobes of the cerebral ganglia; staining of cell bodies elsewhere in the nervous system was capricious. The distribution of NOS-like immunoreactivity differed markedly from that of NADPH diaphorase activity. Small clusters of cells which exhibited NOS-like immunoreactivity were present in the cerebral and pedal ganglia; fibres which exhibited NOS-like immunoreactivity were present in restricted regions of the neuropil of the central ganglia. The disjunct distributions of NADPH diaphorase activity and NOS-like immunoreactivity in the neurvous system of Helix suggest that the properties of neuronal NOS in molluscs may differ sigificantly from those described previously for vertebrate animals.     

Enchancer detector analysis of the extent of genomic involvement in nervous system development in Drosophila melanogaster

We conducted a survey of the patterns of gene expression in the central nervous system (CNS) of larvae of the fruitfly Drosophila melanogaster to identify genes that may be important in the development of the CNS, aid in the recognition of basic organizing features that might underlie CNS development, and estimate the extent of the use of information encoded in the genome in the construction of the nervous system. A so-called enhancer detector strategy was used to generate many thousands of lines containing a β-galactosidase reporter gene. These lines were screened as third-instar larvae for patterns of expression in the developing optic lobes and other portions of the CNS. Most of the lines recovered which evidence staining within the CNS could be included in one of a relatively small number of patterns. A random sample of 594 lines from the larger population screened was selected to quantify the relative frequencies of these patterns, and a more careful analysis of the changes in the patterns of expression with developmental time was done for representative lines of nine of the patterns. These studies demonstrated great variability in the patterns of gene expression as a function of developmental stage. Few, if any, lines showed β-galactosidase activity limited to the optic lobes; similarly, few lines were identified in which staining was limited to only a small number of cells. Together with the limited number of patterns of gene expression seen, this suggests that in the larval CNS developmental pathways may be controlled by a combinatorial process of gene activity that involves the majority of the genome rather than by having a specific gene specify the fate of only a few neuronal precursors. © 1993 John Wiley & Sons, Inc.     

The emergence of neural activity and its role in the development of the enteric nervous system

The enteric nervous system (ENS) is a vital part of the autonomic nervous system that regulates many gastrointestinal functions, including motility and secretion. All neurons and glia of the ENS arise from neural crest-derived cells that migrate into the gastrointestinal tract during embryonic development. It has been known for many years that a subpopulation of the enteric neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development. Recent studies have demonstrated that some enteric neurons exhibit electrical activity from as early as E11.5 in the mouse, with further maturation of activity during embryonic and postnatal development. This article discusses the maturation of electrophysiological and morphological properties of enteric neurons, the formation of synapses and synaptic activity, and the influence of neural activity on ENS development.     

<Emphasis Type="Italic">Hau-Pax6A</Emphasis> expression in the central nervous system of the leech embryo

The leech Helobdella sp. (Austin) has two genes of the Pax6 subfamily, one of which is characterized in detail. Hau-Pax6A was expressed during embryonic development in a pattern similar to other bilaterian animals. RNA was detected in cellular precursors of the central nervous system (CNS) and in peripheral cells including a population associated with the developing eye. The CNS of the mature leech is a ventral nerve cord composed of segmental ganglia, and embryonic Hau-Pax6A expression was primarily localized to the N teloblast lineage that generates the majority of ganglionic neurons. Expression began when the ganglion primordia were four cells in length and was initially restricted to a single cell, n_s.a, whose descendants will form the ganglion’s anterior edge. At later stages, the Hau-Pax6A expression pattern expanded to include additional CNS precursors, including some descendants of the O teloblast. Expression persisted through the early stages of ganglion morphogenesis but disappeared from the segmented body trunk at the time of neuronal differentiation. The timing and iterated pattern of Hau-Pax6A expression in the leech embryo suggests that this gene may play a role in the segmental patterning of CNS morphogenesis.