Area Specificity and Topography of Thalamocortical Projections Are Controlled by ephrin/Eph Genes

Dufour, Audrey; Seibt, Julie; Passante, Lara; Depaepe, Vanessa; Ciossek, Thomas; Frisén, Jonas; Kullander, Klas; Flanagan, John G.; Polleux, Franck; Vanderhaeghen, Pierre

doi:10.1016/s0896-6273(03)00440-9

Cited by 216 publications

(258 citation statements)

References 57 publications

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“…In addition, forward signalling-deficient EphA4 EGFP/EGFP mice provide a radial shift in HC afferent innervation pattern comparable to the one observed in ephrin-A5 À / À animals. Given the crucial involvement of ephrin-A5/EphA4 interactions in establishing thalamocortical mapping 13 , we believe that, in the cochlea, the auditory innervation pattern is achieved on a similar model. Indeed, we show that EphA4 þ type I SGNs connect ephrin-A5 À IHCs, whereas despite the presence of repulsive cues in target cells EphA4 À type II SGNs manage to project to ephrin-A5 þ OHCs (Fig.…”

Section: Discussionmentioning

confidence: 98%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

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Section: Discussionmentioning

confidence: 98%

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

et al. 2013

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“…In several systems such as the retinotectal [10,30], the retinothalamic [31] and the thalamocortical [23,24,26,29] ones, ephrinA5 and its receptors have been found to be expressed in opposite gradients on the projections and their target respectively, leading to a repulsive ligand-receptor interaction. An exception to these observations was described in the olfactory system, where high ephrinA5 expressing region is connected by axons containing an important concentration of ephrinA5 receptors.…”

Section: Introductionmentioning

confidence: 99%

EphrinA5 protein distribution in the developing mouse brain

Deschamps¹,

Morel²,

Janet³

et al. 2010

BMC Neurosci

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Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic mapping of connections and to further characterise the mechanisms involved in pathway restoration following cell transplantation in the damaged brain.

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“…In the developing central nervous system, ephrin ligands and their receptors are extensively expressed and contribute to the formation of connections between brain regions (see, for example, Tuzi and Gullick, 1994;Drescher et al, 1995;Gao et al, 1998;Mackarehtschian et al, 1999;Vanderhaeghen et al, 2000;Uziel et al, 2002;Dufour et al, 2003). In order to identify candidate molecules of the Eph/ephrin family, which might contribute to the development of the thalamocortical system, we performed a comprehensive in situ hybridization screening survey for transcripts of all known members of the family at critical developmental stages of the somatosensory and frontal cortical pathways (Niehage et al, 2005).…”

Section: Who Is Who In the Eph/ephrin Familymentioning

confidence: 99%

“…Receptors EphA3, A4, and A5 are present in E13-15 dorsal thalamus forming a gradient of high rostromedial to low caudolateral expression. At the same time, there is a complementary transient gradient of ephrin-A5 expression in the ventral telencephalon (Dufour et al, 2003). This might lead to a presorting of thalamic axons after they leave the thalamus and grow through the ventral telencephalon toward the cortex.…”

Section: Ephrins Direct Thalamic Axons To Find Their Cortical Targetmentioning

confidence: 99%

Connecting thalamus and cortex: The role of ephrins

et al. 2006

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The complex task of wiring up the brain during embryonic development is achieved by a multitude of guidance signals acting in complex combinations to drive growing axons to their proper targets. The somatosensory system provides an extensively studied model system featuring many universal mechanisms of neural development. In rodents, it constitutes an important model to study how precise topographic connections are achieved. Recent evidence suggests that the Eph/ephrin family of guidance molecules is of pivotal importance for the development of the somatosensory system. Members of Eph/ephrin family are thought to be involved in the global presorting of thalamic axons projecting to the cortex, in labeling specific cortical areas for innervation, in providing topographic cues within the target area, and in distinguishing cortical layers for intracortical wiring. The Eph/ephrin system also seems to contribute to the formation of specific corticothalamic feedback projections. So far, the functions of only a few members of the Eph/ephrin family have been examined, but expression analysis indicates complex combinatorial effects of these signaling molecules. Understanding the Eph/ephrin wiring code is expected to yield new insights into the development and plasticity of brain circuits involved in higher functions.

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Area Specificity and Topography of Thalamocortical Projections Are Controlled by ephrin/Eph Genes

Cited by 216 publications

References 57 publications

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

EphrinA5 protein distribution in the developing mouse brain

Connecting thalamus and cortex: The role of ephrins

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