Masking of Eph receptors and ephrins

Sobieszczuk, Dorothy F.; Wilkinson, David G.

doi:10.1016/s0960-9822(99)80296-6

Cited by 28 publications

(22 citation statements)

References 14 publications

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“…This result suggests that expression of ephrinA5 is down-regulated by P11. We also probed sections with an EphA4-Fc fusion protein, which is capable of detecting any ligand to which EphA4 is able to bind (22,23). Binding of EphA4-Fc to spinal cord sections did not reveal any further possible ligand expression above what was already described (data not shown).…”

Section: Ephrina5 Is Differentially Expressed Within Subpopulations Omentioning

confidence: 69%

Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospinal tract

Canty

Greferath²,

Turnley³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Fine movement in the body is controlled by the motor cortex, which signals in a topographically specific manner to neurons in the spinal cord by means of the corticospinal tract (CST). How the correct topography of the CST is established is unknown. To investigate the possibility that the Eph tyrosine kinase receptor EphA4 is involved in this process, we have traced CST axons in mice in which the EphA4 gene has been deleted. The forelimb subpopulation of CST axons is unaffected in the EphA4 ؊/؊ mice, but the hindlimb subpopulation branches too early within the cord, both temporally and spatially. EphA4 shows a dynamic expression pattern in the environment of the developing CST in the spinal cord: high at the time of forelimb branching and down-regulated before hindlimb branching. To examine whether the fore-and hindlimb subpopulations of CST axons respond differently to EphA4 in their environment, neurons from fore-and hindlimb motor cortex were cultured on a substrate containing EphA4. Neurons from the hindlimb cortex showed reduced branching on the EphA4 substrate compared with their forelimb counterparts. Neurons from the hindlimb cortex express ephrinA5, a high-affinity ligand for EphA4, at higher levels compared with forelimb cortex neurons, and this expression is down-regulated before hindlimb branching. Together, these findings suggest that EphA4 regulates topographic mapping of the CST by controlling the branching of CST axons in the spinal cord.motor control ͉ axon guidance ͉ spinal cord ͉ neuronal development F ine voluntary movement is controlled by the motor areas of the cerebral cortex. The motor cortex has a somatotopic arrangement in which different areas control movements of different parts of the body. For those regions of the motor cortex that control movement of the muscles of the trunk and limbs, the cortical commands travel through the brain in the corticospinal tract (CST) to terminate in topographically specific locations along the spinal cord. There are two major termination zones in the spinal cord, in the cervical and lumbar regions, that carry information for the fore-and hindlimbs, respectively. In primates, the CST axons terminate directly on spinal motor neurons and interneurons, whereas in other mammals, termination occurs almost exclusively on interneurons in the dorsal horns. The CST thus provides the most direct route for cortical control of movement and is the longest and largest descending tract from the brain.During development, growing CST axons must navigate long distances through the brain and spinal cord to reach their gray-matter target cells. How they are successfully guided to their target locations in a topographically correct pattern is unknown. In rodents, CST axons descend through the spinal cord in the ventral aspect of the dorsal funiculus (DF). The axons then exit the DF in topographically specific locations along the cord by means of collateral branching. Several in vivo and in vitro explant studies suggest that as-yet-unidentified diffusible and͞or contact-med...

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Section: Ephrina5 Is Differentially Expressed Within Subpopulations Omentioning

confidence: 69%

Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospinal tract

Canty

Greferath²,

Turnley³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…One way in which low-level activation may be achieved is through cis-inhibitory interactions of coexpressed Eph receptors and ephrins (Hornberger et al 1999;Yin et al 2004;Carvalho et al 2006), and it is likely that overlapping expression occurs in many tissues (Sobieszczuk and Wilkinson 1999). Alternatively, adhesion may be increased by overlapping expression of Eph receptor and ephrinB because this coactivates specific pathways within the same cells (Dravis et al 2004).…”

Section: Cell Segregation and Boundary Formationmentioning

confidence: 99%

Molecular Mechanisms of Cell Segregation and Boundary Formation in Development and Tumorigenesis

Batlle¹,

Wilkinson²

2012

Cold Spring Harbor Perspectives in Biology

172

179

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SUMMARYThe establishment and maintenance of precisely organized tissues requires the formation of sharp borders between distinct cell populations. The maintenance of segregated cell populations is also required for tissue homeostasis in the adult, and deficiencies in segregation underlie the metastatic spreading of tumor cells. Three classes of mechanisms that underlie cell segregation and border formation have been uncovered. The first involves differences in cadherin-mediated cell -cell adhesion that establishes interfacial tension at the border between distinct cell populations. A second mechanism involves the induction of actomyosin-mediated contraction by intercellular signaling, such that cortical tension is generated at the border. Third, activation of Eph receptors and ephrins can lead to both decreased adhesion by triggering cleavage of E-cadherin, and to repulsion of cells by regulation of the actin cytoskeleton, thus preventing intermingling between cell populations. These mechanisms play crucial roles at distinct boundaries during development, and alterations in cadherin or Eph/ephrin expression have been implicated in tumor metastasis.

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“…Reverse signalling by ephrins type A is less well characterised and is thought to involve membrane-associated Src-related kinases such as Fyn and Src [38,47]. Interpretation of signals can be further complicated by co-expression of Ephs and ephrins on the same cell, resulting in cis -interactions that have complex modulatory effects on signalling [48,49,50,51,52]. …”

Section: Introduction To Ephs and Ephrinsmentioning

confidence: 99%

Should I Stay or Should I Go? Ephs and Ephrins in Neuronal Migration

Rodger

Salvatore²,

Migani³

2012

Neurosignals

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In neuroscience, Ephs and ephrins are perhaps best known for their role in axon guidance. It was first shown in the visual system that graded expression of these proteins is instrumental in providing molecular coordinates that define topographic maps, particularly in the visual system, but also in the auditory, vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum and other structures. Perhaps unsurprisingly, the role of these proteins in regulating cell-cell interactions also has an impact on cell mobility, with evidence that Eph-ephrin interactions segregate cell populations based on contact-mediated attraction or repulsion. Consistent with these studies, evidence has accumulated that Ephs and ephrins play important roles in the migration of specific cell populations in the developing and adult brain. This review focusses on two examples of neuronal migration that require Eph/ephrin signalling – radial and tangential migration of neurons in cortical development and the migration of newly generated neurons along the rostral migratory stream to the olfactory bulb in the adult brain. We discuss the challenge involved in understanding how cells determine whether they respond to signals by migration or axon guidance.

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Masking of Eph receptors and ephrins

Cited by 28 publications

References 14 publications

Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospinal tract

Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospinal tract

Molecular Mechanisms of Cell Segregation and Boundary Formation in Development and Tumorigenesis

Should I Stay or Should I Go? Ephs and Ephrins in Neuronal Migration

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