The Eph family of receptor tyrosine kinases and their ligands the ephrins play an essential role in the targeting of retinal ganglion cell axons to topographically correct locations in the optic tectum during visual system development. The African claw-toed frog Xenopus laevis is a popular animal model for the study of retinotectal development because of its amenability to live imaging and electrophysiology. Its visual system undergoes protracted growth continuing beyond metamorphosis, yet little is known about ephrin and Eph expression patterns beyond stage 39 when retinal axons first arrive in the tectum. We used alkaline phosphatase fusion proteins of EphA3, ephrin-A5, EphB2, and ephrin-B1 as affinity probes to reveal the expression patterns of ephrin-As, EphAs, ephrin-Bs, and EphBs, respectively. Analysis of brains from stage 40 to adult frog revealed that ephrins and Eph receptors are expressed throughout development. As observed in other species, staining for ephrin-As displayed a high caudal to low rostral expression pattern across the tectum, roughly complementary to the expression of EphAs. In contrast with the prevailing model, EphBs were found to be expressed in the tectum in a high dorsal to low ventral gradient in young animals. In animals with induced binocular tectal innervation, ocular dominance bands of alternating input from the two eyes formed in the tectum; however, ephrin-A and EphA expression patterns were unmodulated and similar to those in normal frogs, confirming that the segregation of axons into eye-specific stripes is not the consequence of a respecification of molecular guidance cues in the tectum.
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[Show abstract][Hide abstract] ABSTRACT: The axonal connections between the retina and its midbrain target, the superior colliculus (SC), is mapped topographically, such that the spatial relationships of cell bodies in the retina are maintained when terminating in the SC. Topographic map development uses a Cartesian mapping system such that each axis of the retina is mapped independently. Along the nasal-temporal mapping axis, EphAs and ephrin-As, are graded molecular cues required for topographic mapping while the dorsal-ventral axis is mapped in part via EphB and ephrin-Bs. Because both Ephs and ephrins are cell surface molecules they can signal in the forward and reverse directions. Eph/ephrin signaling leads to changes in cytoskeletal dynamics that lead to actin depolymerization and endocytosis guiding axons via attraction and repulsion.
Preview · Article · Oct 2011 · Seminars in Cell and Developmental Biology
[Show abstract][Hide abstract] ABSTRACT: Brain connections are organized into topographic maps that are precisely aligned both within and across modalities. This alignment facilitates coherent integration of different categories of sensory inputs and allows for proper sensorimotor transformations. Topographic maps are established and aligned by multistep processes during development, including interactions of molecular guidance cues expressed in gradients; spontaneous activity-dependent axonal and dendritic remodeling; and sensory-evoked plasticity driven by experience. By focusing on the superior colliculus, a major site of topographic map alignment for different sensory modalities, this review summarizes current understanding of topographic map development in the mammalian visual system and highlights recent advances in map alignment studies. A major goal looking forward is to reveal the molecular and synaptic mechanisms underlying map alignment and to understand the physiological and behavioral consequences when these mechanisms are disrupted at various scales. Expected final online publication date for the Annual Review of Neuroscience Volume 36 is July 08, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
No preview · Article · Apr 2013 · Annual Review of Neuroscience
[Show abstract][Hide abstract] ABSTRACT: Topographic maps are utilized in many sensory and motor systems to efficiently transfer information between brain regions. The retina's projection to the superior colliculus has served as a model for the identification of molecular cues and mechanistic strategies by which topographic maps are formed. Evidence from both in vitro and in vivo studies points to graded cell surface cues playing a central role, but support for axon-axon competition and selective degeneration have also been advanced recently. In combination with mathematical models, these studies suggest that topographic maps are established using a complex combination of strategies to ensure precise connectivity.
No preview · Article · Feb 2014 · Current opinion in neurobiology