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1.
We explored how the odor map in the Drosophila antennal lobe is represented in higher olfactory centers, the mushroom body and lateral horn. Systematic single-cell tracing of projection neurons (PNs) that send dendrites to specific glomeruli in the antennal lobe revealed their stereotypical axon branching patterns and terminal fields in the lateral horn. PNs with similar axon terminal fields tend to receive input from neighboring glomeruli. The glomerular classes of individual PNs could be accurately predicted based solely on their axon projection patterns. The sum of these patterns defines an "axon map" in higher olfactory centers reflecting which olfactory receptors provide input. This map is characterized by spatial convergence and divergence of PN axons, allowing integration of olfactory information. 相似文献
2.
A whole-mount, flattened cortex preparation was developed to compare profiles of axonal projections from main olfactory bulb (MOB) and accessory olfactory bulb (AOB) mitral and tufted (M/T) cells. After injections of the anterograde tracer, Phaseolus vulgaris leucoagglutinin, mapping of labeled axons using a Neurolucida system showed that M/T cells in the AOB sent axons primarily to the medial and posterior lateral cortical amygdala, with minimal branching into the piriform cortex. By contrast, M/T cells in the MOB displayed a network of collaterals that branched off the primary axon at several levels of the lateral olfactory tract (LOT). Collaterals emerging from the LOT into the anterior piriform cortex were often observed crossing into the posterior piriform cortex. M/T cells in the dorsal MOB extended fewer collaterals from the primary axon in the rostral LOT than did M/T cells from the anterior or ventral MOB. MOB M/T cells that projected to the medial amygdala did not do so exclusively, also sending collaterals to the anterior cortical amygdala as well as to olfactory cortical regions. This arrangement may be related to the ability of social experience to modify the response of mice to volatile pheromones detected by the main olfactory system. 相似文献
3.
Hitoshi Yamatani Takahiko Kawasaki Sakura Mita Naoyuki Inagaki Tatsumi Hirata 《Developmental neurobiology》2010,70(7):523-537
After the initial primary projection, axons undergo various structural and functional changes to establish mature neural circuits. The changes in protein expression associated with this maturation were investigated in lateral olfactory tract axons using two‐dimensional gel electrophoresis. The most prominent group upregulated during the period consisted of calcium‐dependent membrane‐binding proteins including VILIP1, neurocalcin δ, copine 6, and annexin A6 from three structurally different families. During maturation of primary cultured neurons, annexin A6 gradually became concentrated on the axon initial segment, and its overexpression significantly enhanced axon branching. On the other hand, overexpression of VILIP1 and neurocalcin δ reduced axon outgrowth and branching. The second group upregulated during axon maturation comprised tubulin‐ and microtubule‐binding proteins including CRMP2, guanine deaminase, MAP1B, and fibronectin type3 SPRY domain‐containing protein. Because the maturation of lateral olfactory axons involves massive extension of secondary collateral branches, the augmentation of these proteins during these stages may underlie the drastic restructuring of the axon cytoskeleton. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:523–537, 2010 相似文献
4.
Anosmin-1, defective in the X-linked form of Kallmann syndrome,promotes axonal branch formation from olfactory bulb output neurons 总被引:10,自引:0,他引:10
Soussi-Yanicostas N de Castro F Julliard AK Perfettini I Chédotal A Petit C 《Cell》2002,109(2):217-228
The physiological role of anosmin-1, defective in the X chromosome-linked form of Kallmann syndrome, is not yet known. Here, we show that anti-anosmin-1 antibodies block the formation of the collateral branches of rat olfactory bulb output neurons (mitral and tufted cells) in organotypic cultures. Moreover, anosmin-1 greatly enhances axonal branching of these dissociated neurons in culture. In addition, coculture experiments with either piriform cortex or anosmin-1-producing CHO cells demonstrate that anosmin-1 is a chemoattractant for the axons of these neurons, suggesting that this protein, which is expressed in the piriform cortex, attracts their collateral branches in vivo. We conclude that anosmin-1 has a dual branch-promoting and guidance activity, which plays an essential role in the patterning of mitral and tufted cell axon collaterals to the olfactory cortex. 相似文献
5.
The structure of the olfactory bulb in tadpoles of Xenopus laevis (stages 54-56) was studied using axon tracing (with biocytin or low-weight dextran) and immunocytochemical techniques. Filling the olfactory nerve with biocytin made the nerve layer and the glomeruli visible. Dye injections into the glomerular layer labeled the lateral olfactory tract. Vice versa, dye injections into the lateral olfactory tract made mitral cells and their glomerular branching patterns visible. Anti-GABA antiserum stained periglomerular and granule cells, while the olfactory nerve and mitral cells were labeled by antiglutamate antiserum. We describe the layering, the numbers of cells and glomeruli, and their localization in both the main and the accessory olfactory bulb. 相似文献
6.
In olfactory systems, neuron-glia interactions have been implicated in the growth and guidance of olfactory receptor axons. In the moth Manduca sexta, developing olfactory receptor axons encounter several types of glia as they grow into the brain. Antennal nerve glia are born in the periphery and enwrap bundles of olfactory receptor axons in the antennal nerve. Although their peripheral origin and relationship with axon bundles suggest that they share features with mammalian olfactory ensheathing cells, the developmental roles of antennal nerve glia remain elusive. When cocultured with antennal nerve glial cells, olfactory receptor growth cones readily advance along glial processes without displaying prolonged changes in morphology. In turn, olfactory receptor axons induce antennal nerve glial cells to form multicellular arrays through proliferation and process extension. In contrast to antennal nerve glia, centrally derived glial cells from the axon sorting zone and antennal lobe never form arrays in vitro, and growth-cone glial-cell encounters with these cells halt axon elongation and cause permanent elaborations in growth cone morphology. We propose that antennal nerve glia play roles similar to olfactory ensheathing cells in supporting axon elongation, yet differ in their capacity to influence axon guidance, sorting, and targeting, roles that could be played by central olfactory glia in Manduca. 相似文献
7.
The Drosophila ortholog of the Zc3h14 RNA binding protein acts within neurons to pattern axon projection in the developing brain
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Seth M. Kelly Rick Bienkowski Ayan Banerjee David J. Melicharek Zachariah A. Brewer Daniel R. Marenda Anita H. Corbett Kenneth H. Moberg 《Developmental neurobiology》2016,76(1):93-106
The dNab2 polyadenosine RNA binding protein is the D. melanogaster ortholog of the vertebrate ZC3H14 protein, which is lost in a form of inherited intellectual disability (ID). Human ZC3H14 can rescue D. melanogaster dNab2 mutant phenotypes when expressed in all neurons of the developing nervous system, suggesting that dNab2/ZC3H14 performs well‐conserved roles in neurons. However, the cellular and molecular requirements for dNab2/ZC3H14 in the developing nervous system have not been defined in any organism. Here we show that dNab2 is autonomously required within neurons to pattern axon projection from Kenyon neurons into the mushroom bodies, which are required for associative olfactory learning and memory in insects. Mushroom body axons lacking dNab2 project aberrantly across the brain midline and also show evidence of defective branching. Coupled with the prior finding that ZC3H14 is highly expressed in rodent hippocampal neurons, this requirement for dNab2 in mushroom body neurons suggests that dNab2/ZC3H14 has a conserved role in supporting axon projection and branching. Consistent with this idea, loss of dNab2 impairs short‐term memory in a courtship conditioning assay. Taken together these results reveal a cell‐autonomous requirement for the dNab2 RNA binding protein in mushroom body development and provide a window into potential neurodevelopmental functions of the human ZC3H14 protein. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 93–106, 2016 相似文献
8.
During development, growth cones direct growing axons into appropriate targets. However, in some cortical pathways target innervation occurs through the development of collateral branches that extend interstitially from the axon shaft. How do such branches form? Direct observations of living cortical brain slices revealed that growth cones of callosal axons pause for many hours beneath their cortical targets prior to the development of interstitial branches. High resolution imaging of dissociated living cortical neurons for many hours revealed that the growth cone demarcates sites of future axon branching by lengthy pausing behaviors and enlargement of the growth cone. After a new growth cone forms and resumes forward advance, filopodial and lamellipodial remnants of the large paused growth cone are left behind on the axon shaft from which interstitial branches later emerge. To investigate how the cytoskeleton reorganizes at axon branch points, we fluorescently labeled microtubules in living cortical neurons and imaged the behaviors of microtubules during new growth from the axon shaft and the growth cone. In both regions microtubules reorganize into a more plastic form by splaying apart and fragmenting. These shorter microtubules then invade newly developing branches with anterograde and retrograde movements. Although axon branching of dissociated cortical neurons occurs in the absence of targets, application of a target-derived growth factor, FGF-2, greatly enhances branching. Taken together, these results demonstrate that growth cone pausing is closely related to axon branching and suggest that common mechanisms underlie directed axon growth from the terminal growth cone and the axon shaft. 相似文献
9.
Crandall JE Dibble C Butler D Pays L Ahmad N Kostek C Püschel AW Schwarting GA 《Journal of neurobiology》2000,45(4):195-206
In early rat embryos when axons from sensory neurons first contact the olfactory bulb primordium, lactosamine-containing glycans (LCG) are detected on neurons that are broadly distributed within the olfactory epithelium, but that project axons to a very restricted region of the ventromedial olfactory bulb. LCG(+) axons extend through channels defined by the coexpression of galectin-1 and beta2-laminin. These two extracellular matrix molecules are differentially expressed, along with semaphorin 3A, by subsets of ensheathing cells in the ventral nerve layer of the olfactory bulb. The overlapping expression of these molecules creates an axon-sorting domain that is capable of promoting and repelling subsets of olfactory axons. Specifically, LCG(+) axons preferentially grow into the region of the nerve layer that expresses high amounts of galectin-1, beta2-laminin, and semaphorin 3A, whereas neuropilin-1(+) axons grow in a complementary pattern, avoiding the ventral nerve layer and projecting medially and laterally. These studies suggest that initial patterning of olfactory epithelium to olfactory bulb connections is, in part, dependent on extracellular components of the embryonic nerve layer that mediate convergence and divergence of specific axon subsets. 相似文献
10.
Semaphorins are a large class of proteins that function throughout the nervous system to guide axons. It had previously been shown that Semaphorin 5A (Sema5A) was a bifunctional axon guidance cue for mammalian midbrain neurons. We found that zebrafish sema5A was expressed in myotomes during the period of motor axon outgrowth. To determine whether Sema5A functioned in motor axon guidance, we knocked down Sema5A, which resulted in two phenotypes: a delay in motor axon extension into the ventral myotome and aberrant branching of these motor axons. Both phenotypes were rescued by injection of full-length rat Sema5A mRNA. However, adding back RNA encoding the sema domain alone significantly rescued the branching phenotype in sema5A morphants. Conversely, adding back RNA encoding the thrombospondin repeat (TSR) domain alone into sema5A morphants exclusively rescued delay in ventral motor axon extension. Together, these data show that Sema5A is a bifunctional axon guidance cue for vertebrate motor axons in vivo. The TSR domain promotes growth of developing motor axons into the ventral myotome whereas the sema domain mediates repulsion and keeps these motor axons from branching into surrounding myotome regions. 相似文献
11.
M. Wachowiak B. W. Ache 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1994,175(1):35-48
Whole-cell patch-clamp recording was used to characterize olfactory projection neurons in an isolated brain preparation of the spiny lobster, Panulirus argus. Responses to electrical stimulation of the olfactory afferents were recorded from projection neuron somata using biocytin-filled electrodes. All projection neurons were multiglomerular, innervating up to 80% of all olfactory lobe glomeruli, but the innervation was heterogeneous. Most neurons densely innervated only 3–4 glomeruli; the remaining glomeruli in their dendritic arbor were sparsely innervated, thereby creating two distinct patterns of intraglomerular branching. Projection neurons responded to orthodromic stimulation with an initial depolarization and spiking followed by a 1–3 s hyperpolarization. The inhibitory phase of the response was lower in threshold and longer in latency than the excitatory phase, a response pattern also reported in olfactory projection neurons of insects and vertebrates. The somata of the projection neurons supported voltage-activated currents and TTX-sensitive action potentials, suggesting that the soma, although spatially separated from the axon and dendrites, may play a significant functional role in these cells. Dye coupling between some projection neurons correlated with the presence of multiple amplitude action potentials, suggesting that at least some projection neurons may be coupled via gap junctions. 相似文献
12.
Axon branching is vital to the development of a highly interconnected and functional nervous system. Similar to axon growth and guidance, axon branching is subject to dynamic remodeling of the neuronal cytoskeleton. Coordinated remodeling of the cytoskeleton is achieved through parallel and direct targeting of both actin filaments and a subset of highly dynamic microtubules that probe the actin-rich peripheral domains in growth cones and emerging branch sites. A growing number of extracellular cues implicated in growth cone guidance also influence axon branch behavior. Mechanistic insight into the molecular basis of growth cone steering and axon branching reveals significant similarities but also uncovers important differences between these crucial events in the establishment of neural circuits. 相似文献
13.
Background
Although originally identified as embryonic axon guidance cues, semaphorins are now known to regulate multiple, distinct, processes crucial for neuronal network formation including axon growth and branching, dendritic morphology, and neuronal migration. Semaphorin7A (Sema7A), the only glycosylphosphatidylinositol-anchored semaphorin, promotes axon growth in vitro and is required for the proper growth of the mouse lateral olfactory tract in vivo. Sema7A has been postulated to signal through two unrelated receptors, an RGD-dependent α1β1-integrin and a member of the plexin family, plexinC1. β1-integrins underlie Sema7A-mediated axon growth and Sema7A function in the immune system. Sema7A-plexinC1 interactions have also been implicated in immune system function, but the neuronal role of this ligand-receptor pair remains to be explored. To gain further insight into the function(s) of Sema7A and plexinC1 during neural development, we present here a detailed analysis of Sema7A and plexinC1 expression in the developing rat nervous system. 相似文献14.
15.
The olfactory system presents a practical model for investigating basic mechanisms involved in patterning connections between peripheral sensory neurons and central targets. Our understanding of olfactory map formation was advanced greatly by the discovery of cAMP signaling as an important determinant of glomerular positioning in the olfactory bulb. Additionally, several cell adhesion molecules have been identified recently that are proposed to regulate homotypic interactions among projecting axons. From these studies a model has emerged to partially explain the wiring of axons from widely dispersed neuron populations in the nasal cavity to relatively stereotyped glomerular positions. These advances have revitalized interest in axon guidance molecules in establishing olfactory topography, but also open new questions regarding how these patterns of guidance cues are established and function, and what other pathways, such as glycosylation, might be involved. This review summarizes the current state of this field and the important molecules that impact on cAMP-dependent mechanism in olfactory axon guidance. 相似文献
16.
Rugarli EI Di Schiavi E Hilliard MA Arbucci S Ghezzi C Facciolli A Coppola G Ballabio A Bazzicalupo P 《Development (Cambridge, England)》2002,129(5):1283-1294
Kallmann syndrome is an inherited disorder defined by the association of anosmia and hypogonadism, owing to impaired targeting and migration of olfactory axons and gonadotropin-releasing hormone secreting neurons. The gene responsible for the X-linked form of Kallmann syndrome, KAL-1, encodes a secreted protein of still elusive function. It has been proposed that KAL-1 might be involved in some aspects of olfactory axon guidance. However, the unavailability of a mouse model, and the difficulties in studying cellular and axonal migration in vertebrates have hampered an understanding of its function. We have identified the C. elegans homolog, kal-1, and document its function in vivo. We show that kal-1 is part of a mechanism by which neurons influence migration and adhesion of epidermal cells undergoing morphogenesis during ventral enclosure and male tail formation. We also show that kal-1 affects neurite outgrowth in vivo by modulating branching. Finally, we find that human KAL-1 cDNA can compensate for the loss of worm kal-1 and that overexpression of worm or human KAL-1 cDNAs in the nematode results in the same phenotypes. These data indicate functional conservation between the human and nematode proteins and establish C. elegans as a powerful animal in which to investigate KAL function in vivo. Our findings add a new player to the set of molecules, which appear to underlie both morphogenesis and axonal/neuronal navigation in vertebrates and invertebrates. 相似文献
17.
Cortney C. Winkle Leslie M. McClain Juli G. Valtschanoff Charles S. Park Christopher Maglione Stephanie L. Gupton 《The Journal of cell biology》2014,205(2):217-232
Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion. 相似文献
18.
Letizia Marvaldi Barbara Hausott Maria Auer Johann Leban Lars Klimaschewski 《Neurochemical research》2014,39(2):403-407
Recently, a new potent protein kinase inhibitor, SC82510, was identified acting on DRAK2 and stimulating axon outgrowth at low concentrations. DRAK is the Drosophila homologue of death-associated protein kinase that phosphorylates myosin-II regulatory light chain in a similar fashion as ROCK, the downstream target of RhoA mediating axon outgrowth inhibition. While higher concentrations of this novel compound exhibited toxic effects, significant promotion of process outgrowth of PC12 cells and of adult primary neurons was observed at 1 nM which could be further enhanced by addition of a neuronal growth factor (FGF-2). Unlike the effects of ROCK inhibitors on axon outgrowth that stimulate both, elongation and branching, SC82510 primarily promoted axon branching, whereas axon elongation was not increased in this cell culture model of peripheral axon regeneration. 相似文献
19.
In the olfactory system of Drosophila, 50 functional classes of sensory receptor neurons (ORNs) project in a highly organized fashion into the CNS, where they sort out from one another and converge into distinct synaptic glomeruli. We identified the transmembrane molecule Semaphorin-1a (Sema-1a) as an essential component to ensure glomerulus-specific axon segregation. Removal of sema-1a in ORNs does not affect the pathfinding toward their target area but disrupts local axonal convergence into a single glomerulus, resulting in two distinct targeting phenotypes: axons either intermingle with adjacent ORN classes or segregate according to their odorant receptor identity into ectopic sites. Differential Sema-1a expression can be detected among neighboring glomeruli, and mosaic analyses show that sema-1a functions nonautonomously in ORN axon sorting. These findings provide insights into the mechanism by which afferent interactions lead to synaptic specificity in the olfactory system. 相似文献
20.
1. Single unimodal (olfactory) or multimodal (olfactory and mechanosensory) neurons in the antennal lobe of the deutocerebrum of the American cockroach were characterized functionally by microelectrode recording, and their morphological types and positions in the brain were established by dye injection. Thus individual, physiologically identified neurons of known shape could be mapped in reference to the areas of soma groups, glomeruli, tracts and their projection regions in the brain. 2. All of these neurons send processes to deutocerebral glomeruli, i.e., the regions in which the axons of antennal sensory cells terminate. Output neurons have axons that leave the deutocerebrum whereas local interneurons are anaxonic. 3. An output neuron innervates only one glomerulus, sending its axon into the calyces of the corpora pedunculata (CP) in the protocerebrum, where by multiple branching they reach many CP neurons. The same axons send collaterals into the lateral lobe of the protocerebrum. Because of this arrangement, each deutocerebral glomerulus is represented individually and separately in the two projection regions. The fine structure of the endings of the deutocerebral axons in the protocerebrum is described. In the CP calyces they form microglomeruli with typical divergent connectivity. 4. A local interneuron innervates many glomeruli without sending processes to other parts of the brain. 5. Unimodal olfactory and multimodal neurons can be either output neurons or local interneurons; multimodal information is sent to the protocerebrum directly, in parallel with the unimodal information. 6. At least one glomerulus--the macroglomerulus of the male deutocerebrum--is specialized so as to provide an exclusive topographic representation of certain olfactory stimuli not represented elsewhere (female sexual pheromone). 相似文献