Robos and Slits Control the Pathfinding and Targeting of Mouse Olfactory Sensory Axons

Nguyen-Ba-Charvet, Kim T.; Meglio, Thomas Di; Fouquet, Coralie; Chédotal, Alain

doi:10.1523/jneurosci.5671-07.2008

Cited by 73 publications

(81 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1A,B). Consistent with previous reports (Nguyen-Ba-Charvet et al, 2008), immunostaining in E16 brain sections from mice showed that Slit-2 was highly expressed in apical cells of the OE (Fig. 1D).…”

Section: Robo1 Is Expressed In Oecs Both In Vitro and In Vivosupporting

confidence: 92%

“…Recent studies have shown that glial cell migration can also be directed by some axon guidance molecules (Tsai and Miller, 2002). Because OECs share a common origin (olfactory placode) with olfactory sensory neurons and migrate out from the OE to the OB together with olfactory sensory axons during the same developing period (Valverde et al, 1992), it is likely that guidance cues for olfactory sensory axons, like Slit (Cho et al, 2007;Nguyen-Ba-Charvet et al, 2008), might also guide the migration and distribution of OECs.…”

Section: Discussionmentioning

confidence: 99%

“…Slit was first identified in Drosophila as a molecule secreted by midline cells, and was later shown to repel the extension of axons expressing Robo receptors (Brose et al, 1999;Kidd et al, 1999;Seeger et al, 1993) and to regulate the migration of cells such as neuronal precursors . In the olfactory system, members of the Slit and Robo families are expressed in a specific spatiotemporal pattern and play important roles in the guidance of olfactory sensory axons (Cho et al, 2007;Marillat et al, 2002;Nguyen-Ba-Charvet et al, 2008;Yuan et al, 1999). Whether OECs, which have the same developmental origin as olfactory sensory neurons, are also responsive to Slits is unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Huang

Wang

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryOlfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca 2+ release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca 2+ -dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca 2+ and cofilin signaling during Slit-2-triggered repulsion.

show abstract

Section: Robo1 Is Expressed In Oecs Both In Vitro and In Vivosupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Huang

Wang

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In robo2 mutant zebrafish, glomerular spatial arrangements in the main olfactory system are also impaired (Miyasaka et al, 2005). The mistargeting of OSN axons is even more obvious in Robo1/Robo2 and Slit1/Slit2 double-null mice, in which OSNs that express the same odorant receptors project on to multiple glomeruli (Nguyen-Ba-Charvet et al, 2008) (Fig. 3C).…”

Section: Reviewmentioning

confidence: 97%

Moving away from the midline: new developments for Slit and Robo

2010

View full text Add to dashboard Cite

SummaryIn most tissues, the precise control of cell migration and cellcell interaction is of paramount importance to the development of a functional structure. Several families of secreted molecules have been implicated in regulating these aspects of development, including the Slits and their Robo receptors. These proteins have well described roles in axon guidance but by influencing cell polarity and adhesion, they participate in many developmental processes in diverse cell types. We review recent progress in understanding both the molecular mechanisms that modulate Slit/Robo expression and their functions in neural and non-neural tissue. Key words: Axon guidance, Cell migration, Cell-cell interaction IntroductionIn most organisms, the central nervous system (CNS) develops along a bilateral axis of symmetry located at the midline (Placzek and Briscoe, 2005). During development, the ventral midline or floor plate acts as an organiser through the secretion of diffusible proteins (Placzek and Briscoe, 2005;Gore et al., 2008), which control the growth of axons and dendrites and the migration of neurons across the midline. In the forebrain, glial or neuronal cells delineate the midline (see Glossary, Box 1) and also control axon guidance. For more than two decades, many developmental neurobiologists have tried to understand the mechanisms that control midline crossing in the CNS and to answer some key questions. Firstly, how are commissural axons (see Glossary, Box 1) attracted to the midline and how do their growth cones (see Glossary, Box1) receive and integrate the multiple and contrasting signals released by midline cells? Secondly, what are the molecular and signalling changes that enable commissural axons to leave the midline and often to switch to a longitudinal growth mode? All midline-derived axon guidance factors are expressed at other locations in many developing and mature tissues, where they control a wide range of biological processes.Roundabout receptors (Robo) and their Slit ligands form one of the most crucial ligand-receptor pairings among the axon guidance molecules. Robos were identified in Drosophila in a mutant screen for genes that control the midline crossing of commissural axons (Kidd et al., 1998;Seeger et al., 1993). Similarly, Slit was discovered in Drosophila as a protein secreted by midline glia (Rothberg et al., 1988;Rothberg et al., 1990). Homologues of both proteins have since been discovered in many species (for a review, see . However, the Slit/Robo couple not only functions in axon guidance but also in a variety of developmental Development 137, 1939Development 137, -1952Development 137, (2010 Commissural axons Axons with cell bodies (somata) located on one side of the central nervous system (CNS) that project axons across the midline to contact target cells on the opposite side. Growth cone A specialised bulbous enlargement at the end of growing axons that is characterised by dynamic filamentous extensions, known as filopodia. They sense the environment and respond to adhesi...

show abstract

“…1B). Mice deficient for Robo-2 have defective axonal projections along the D-V axis (Cho et al 2007;Nguyen-Ba-Charvet et al 2008).…”

Section: Mechanisms Of Olfactory Map Formation In Mammals Topographicmentioning

confidence: 99%

Topographic Mapping--The Olfactory System

Imai¹,

Sakano²,

Vosshall³

2010

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils-the olfactory glomeruli-that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.T he olfactory system detects airborne organic and inorganic chemicals that originate from plant and animal metabolites and environmental and industrial sources. Odors mediate both innate and learned behaviors such as attraction and aversion, governing decisions to eat, mate, attack or flee from aggressors and predators. A remarkable feature of the olfactory system is the extraordinary diversity of possible odor molecules that exist. Although accurate measurements can be made of the detection range of visual wavelengths or auditory frequencies in humans, there are no reliable estimates of the number of odorous molecules that exist on earth or those that can be detected by a given animal species (Gilbert 2008). Nevertheless, the number of possible odorants is thought to be high, in the range of many thousands. Beyond odor detection lies the problem of odor discrimination: how can chemicals with slightly different physical properties be discriminated and associated with distinct odor percepts?Experiments investigating the molecular logic of olfaction over the last 20 years have led to major insights into how animals solve the problem of detecting and discriminating a vast number of different odor stimuli (Axel 1995). Four organizational principles have emerged from this work. First, large numbers of distinct odorant receptor (OR) genes are dedicated

show abstract

Robos and Slits Control the Pathfinding and Targeting of Mouse Olfactory Sensory Axons

Cited by 73 publications

References 34 publications

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition

Moving away from the midline: new developments for Slit and Robo

Topographic Mapping--The Olfactory System

Contact Info

Product

Resources

About