Receptor protein tyrosine phosphatases regulate retinal ganglion cell axon outgrowth in the developing Xenopus visual system.
Receptor protein tyrosine phosphatases (RPTPs) are regulators of axon outgrowth and guidance in a variety of different vertebrate and invertebrate systems. Three RPTPs, CRYP-alpha, PTP-delta, and LAR, are expressed in overlapping but distinct patterns in the developing Xenopus retina, including expression in retinal ganglion cells (RGCs) as they send axons to the tectum (Johnson KG, Holt CE. 2000. Expression of CRYP-alpha, LAR, PTP-delta, and PTP-rho in the developing Xenopus visual system. Mech Dev 92:291-294). In order to examine the role of these RPTPs in visual system development, putative dominant negative RPTP mutants (CS-CRYP-alpha, CS-PTP-delta, and CS-LAR) were expressed either singly or in combination in retinal cells. No effect was found on either retinal cell fate determination or on gross RGC axon guidance to the tectum. However, expression of these CS-RPTP constructs differentially affected the rate of RGC axon outgrowth. In vivo, expression of all three CS-RPTPs or CS-PTP-delta alone inhibited RGC axon outgrowth, while CS-LAR and CS-CRYP-alpha had no significant effect. In vitro, expression of CS-CRYP-alpha enhanced neurite outgrowth, while CS-PTP-delta inhibited neurite outgrowth in a substrate-dependent manner. This study provides the first in vivo evidence that RPTPs regulate retinal axon outgrowth.
Johnson
K G
KG
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, United Kingdom. karl_johnson@hms.harvard.edu
McKinnell
I W
IW
Stoker
A W
AW
Holt
C E
CE
D000818:Animals; D030161:Avian Proteins; D001369:Axons / Q000502:physiology*; D001757:Blastomeres; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D008845:Microinjections; D008954:Models, Biological; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000502:physiology; D009900:Optic Nerve / Q000196:embryology* / Q000201:enzymology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D054557:Receptor-Like Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012160:Retina / Q000637:transplantation; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000201:enzymology; D013477:Superior Colliculi / Q000196:embryology* / Q000201:enzymology; D014795:Visual Pathways / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
D030161:Avian Proteins; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D011505:Protein-Tyrosine Kinases; C490606:CRYPalpha protein, Gallus gallus; C094525:CRYPalpha protein, Xenopus; D017027:Protein Tyrosine Phosphatases; C490394:Ptprd protein, Xenopus; D054557:Receptor-Like Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2