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Publication : Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map.

First Author  Yoo S Year  2011
Journal  EMBO J Volume  30
Issue  8 Pages  1593-607
PubMed ID  21343910 Mgi Jnum  J:171255
Mgi Id  MGI:4949044 Doi  10.1038/emboj.2011.44
Citation  Yoo S, et al. (2011) Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map. EMBO J 30(8):1593-607
abstractText  Endocytosis of Eph-ephrin complexes may be an important mechanism for converting cell-cell adhesion to a repulsive interaction. Here, we show that an endocytosis-defective EphA8 mutant forms a complex with EphAs and blocks their endocytosis in cultured cells. Further, we used bacterial artificial chromosome transgenic (Tg) mice to recapitulate the anterior>posterior gradient of EphA in the superior colliculus (SC). In mice expressing the endocytosis-defective EphA8 mutant, the nasal axons were aberrantly shifted to the anterior SC. In contrast, in Tg mice expressing wild-type EphA8, the nasal axons were shifted to the posterior SC, as predicted for the enhanced repellent effect of ephrinA reverse signalling. Importantly, Rac signalling was shown to be essential for EphA-ephrinA internalization and the subsequent nasal axonal repulsion in the SC. These results indicate that endocytosis of the Eph-ephrin complex is a key mechanism by which axonal repulsion is generated for proper guidance and topographic mapping.
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