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The Journal of Neuroscience, January 18, 2006, 26(3):882-892; doi:10.1523/JNEUROSCI.3162-05.2006

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

Shannon W. Mendes,¹ Mark Henkemeyer,² and Daniel J. Liebl^1,3

¹Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida 33136, ²Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390, and ³The Miami Project to Cure Paralysis and Department of Neurosurgery, University of Miami School of Medicine, Miami, Florida 33136

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.

Key words: ephrins; Eph receptors; corpus callosum; midline guidance; mouse development; glial wedge

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Received July 29, 2005; revised November 11, 2005; accepted December 2, 2005.

This article has been cited by other articles:

				T. M. Coate, J. A. Wirz, and P. F. Copenhaver Reverse Signaling via a Glycosyl-Phosphatidylinositol-Linked Ephrin Prevents Midline Crossing by Migratory Neurons during Embryonic Development in Manduca J. Neurosci., April 9, 2008; 28(15): 3846 - 3860. [Abstract] [Full Text] [PDF]

				S. R. Kadison, T. Makinen, R. Klein, M. Henkemeyer, and Z. Kaprielian EphB Receptors and Ephrin-B3 Regulate Axon Guidance at the Ventral Midline of the Embryonic Mouse Spinal Cord. J. Neurosci., August 30, 2006; 26(35): 8909 - 8914. [Abstract] [Full Text] [PDF]

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