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© The Rockefeller University Press, 0021-9525/1999//375 $5.00
The Journal of Cell Biology, Volume 147, Number 2, , 1999 375-388

Original Article

The Receptor Tyrosine Phosphatase Cryp{alpha} Promotes Intraretinal Axon Growth



Matthias M. Lediga, Fawaz Hajb, John L. Bixbyc, Andrew W. Stokerb, and Bernhard K. Muellera

a Max-Planck-Institut für Entwicklungsbiologie, Physikalische Biologie, D-72076 Tübingen, Germany
b Institute of Child Health, Neural Development Unit, University College London, London WC1N 1EH, United Kingdom
c Department of Molecular and Cellular Pharmacology and Neuroscience Program, University of Miami School of Medicine, Miami, Florida 33101
Max-Planck-Institut für Entwicklungsbiologie, Abteilung I, Physikalische Biologie, Spemannstr. 35/I, D-72076 Tübingen, Germany.49-7071-601-30549-7071-601-341

bernhard.mueller{at}tuebingen.mpg.de

Retinal ganglion cell axons grow towards the optic fissure in close contact with the basal membrane, an excellent growth substratum. One of the ligands of receptor tyrosine phosphatase CRYP{alpha} is located on the retinal and tectal basal membranes. To analyze the role of this RPTP and its ligand in intraretinal growth and guidance of ganglion cell axons, we disrupted ligand- receptor interactions on the retinal basal membrane in culture. Antibodies against CRYP{alpha} strongly reduced retinal axon growth on the basal membrane, and induced a dramatic change in morphology of retinal growth cones, reducing the size of growth cone lamellipodia. A similar effect was observed by blocking the ligand with a CRYP{alpha} ectodomain fusion protein. These effects did not occur, or were much reduced, when axons were grown either on laminin-1, on matrigel or on basal membranes with glial endfeet removed. This indicates that a ligand for CRYP{alpha} is located on glial endfeet. These results show for the first time in vertebrates that the interaction of a receptor tyrosine phosphatase with its ligand is crucial not only for promotion of retinal axon growth but also for maintenance of retinal growth cone lamellipodia on basal membranes.

Key Words: receptor protein tyrosine phosphatase • axon growth • actin cytoskeleton • growth cone • integrin

© 1999 The Rockefeller University Press

1.used in this paper: AP, alkaline phosphatase; BM, basal membrane, BM-Ef, basal membranes with endfeet removed; ECM, extracellular matrix; LN, laminin; PLL, poly-l-lysine; RPTP, receptor protein tyrosine phosphatase

Dr. Haj's present address is Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215.


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