Ephrin-B2 and EphB1 Mediate Retinal Axon Divergence at the Optic Chiasm

Williams, Scott; Mann, Fanny; Erskine, Lynda; Sakurai, Takeshi; Wei, Shiniu; Rossi, Derrick J.; Gale, Nicholas W.; Holt, Christine; Mason, Carol A.; Henkemeyer, Mark

doi:10.1016/j.neuron.2003.08.017

Cited by 320 publications

(403 citation statements)

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“…2c). This discrete region of the subventricular zone and cortex is thought to represent projecting radial glia (Shu et al, 2003b;Williams et al, 2003), which was confirmed by immunohistochemistry with the radial glia marker anti-RC1 (Fig. 2d).…”

Section: Expression Of Ephrins In the Developing Forebrainmentioning

confidence: 58%

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Mendes¹,

Henkemeyer²,

Liebl³

2006

J. Neurosci.

105

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Agenesis of the corpus callosum (CC) is a rare birth defect that occurs in isolated conditions and in combination with other developmental cerebral abnormalities. Recent identification of families of growth and guidance molecules has generated interest in the mechanisms that regulate callosal growth. One family, ephrins and Eph receptors, has been implicated in mediating midline pathfinding decisions; however, the complexity of these interactions has yet to be unraveled. Our studies shed light on which B-class ephrins and Eph receptors function to regulate CC midline growth and how these molecules interact with important guideposts during development. We show that multiple Eph receptors (B1, B2, B3, and A4) and B-class ephrins (B1, B2, and B3) are present and function in developing forebrain callosal fibers based on both spatial and temporal expression patterns and analysis of gene-targeted knock-out mice. Defects are most pronounced in the combination double knock-out mice, suggesting that compensatory mechanisms exist for several of these family members. Furthermore, these CC defects range from mild hypoplasia to complete agenesis and Probst's bundle formation. Further analysis revealed that Probst's bundle formation may reflect aberrant glial formations and/or altered sensitivity of CC axons to other guidance cues. Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing and human disorder.

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Section: Expression Of Ephrins In the Developing Forebrainmentioning

confidence: 58%

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Mendes¹,

Henkemeyer²,

Liebl³

2006

J. Neurosci.

105

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“…All EphB mutant mice were previously described (23)(24)(25)44). EphrinB1 loxp and EphrinB2 loxp cKO mice were previously described (32,45).…”

Section: Methodsmentioning

confidence: 99%

EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon pathfinding

Robichaux

Chenaux

et al. 2014

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

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In early brain development, ascending thalamocortical axons (TCAs) navigate through the ventral telencephalon (VTel) to reach their target regions in the young cerebral cortex. Descending, deep-layer cortical axons subsequently target appropriate thalamic and subcortical target regions. However, precisely how and when corticothalamic axons (CTAs) identify their appropriate, reciprocal thalamic targets remains unclear. We show here that EphB1 and EphB2 receptors control proper navigation of a subset of TCA and CTA projections through the VTel. We show in vivo that EphB receptor forward signaling and the ephrinB1 ligand are required during the early navigation of L1-CAM + thalamic fibers in the VTel, and that the misguided thalamic fibers in EphB1/2 KO mice appear to interact with cortical subregion-specific axon populations during reciprocal cortical axon guidance. As such, our findings suggest that descending cortical axons identify specific TCA subpopulations in the dorsal VTel to coordinate reciprocal corticalthalamic connectivity in the early developing brain.

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“…Retinal ganglion cells in the ventrotemporal retinal crescent project ipsilaterally, whereas ganglion cells outside of the ventrotemporal retina and some late-born cells in the ventrotemporal retina project contralaterally (Godement et al 1990;Guillery et al 1995). In both the frog and mouse, ephrinBs expressed by glial cells at the midline force ventrotemporal retinal ganglion cell axons expressing EphB receptors to the ipsilateral side of the chiasm (Nakagawa et al 2000;Williams et al 2003). The timing of receptor and ligand expression and subsequent downregulation is exquisite (Williams et al 2003).…”

Section: Distribution and Regulation Of Guidance Receptors And Cuesmentioning

confidence: 99%

“…In both the frog and mouse, ephrinBs expressed by glial cells at the midline force ventrotemporal retinal ganglion cell axons expressing EphB receptors to the ipsilateral side of the chiasm (Nakagawa et al 2000;Williams et al 2003). The timing of receptor and ligand expression and subsequent downregulation is exquisite (Williams et al 2003). The transcription factor Zic2 regulates EphB1 expression in ventrotemporal retinal ganglion cells, it is required for the ipsilateral projection, and it is sufficient to induce an ipsilateral…”

Section: Distribution and Regulation Of Guidance Receptors And Cuesmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

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Ephrin-B2 and EphB1 Mediate Retinal Axon Divergence at the Optic Chiasm

Cited by 320 publications

References 50 publications

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon pathfinding

Cellular Strategies of Axonal Pathfinding

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