RESUMEN
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.
Asunto(s)
Proteínas Aviares , Axones/fisiología , Moléculas de Adhesión Celular/fisiología , Proteínas del Ojo/fisiología , Proteínas del Tejido Nervioso , Nervio Óptico/embriología , Proteínas Tirosina Fosfatasas/fisiología , Proteínas Tirosina Quinasas/fisiología , Receptores de Superficie Celular/fisiología , Células Ganglionares de la Retina/citología , Colículos Superiores/embriología , Vías Visuales/embriología , Proteínas de Xenopus , Xenopus laevis/embriología , Animales , Blastómeros , Moléculas de Adhesión Celular/genética , Embrión de Pollo , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Proteínas del Ojo/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Genes Dominantes , Microinyecciones , Modelos Biológicos , Familia de Multigenes , Mutagénesis Sitio-Dirigida , Neuritas/fisiología , Nervio Óptico/enzimología , Técnicas de Cultivo de Órganos , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Fosfatasas Similares a Receptores , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores , Receptores de Superficie Celular/genética , Proteínas Recombinantes de Fusión/fisiología , Retina/trasplante , Células Ganglionares de la Retina/enzimología , Colículos Superiores/enzimología , Vías Visuales/citología , Vías Visuales/enzimología , Xenopus laevis/metabolismoRESUMEN
Receptor tyrosine kinases and receptor protein tyrosine phosphatases (RPTPs) appear to coordinate many aspects of neural development, including axon growth and guidance. Here, we focus on the possible roles of RPTPs in the developing avian retinotectal system. Using both in situ hybridization analysis and immunohistochemistry, we show for the first time that five RPTP genes--CRYPalpha, CRYP-2, PTPmu, PTPgamma, and PTPalpha--have different but overlapping expression patterns throughout the retina and the tectum. PTPalpha is restricted to Muller glia cells and radial glia of the tectum, indicating a possible function in controlling neuronal migration. PTPgamma expression is restricted to amacrine neurons. CRYPalpha and CRYP-2 mRNAs in contrast are expressed throughout the retinal ganglion cell layer from where axons grow out to their tectal targets. PTPmu is expressed in a subset of these ganglion cells. CRYPalpha, CRYP-2, and PTPmu proteins are also localized in growth cones of retinal ganglion cell axons and are present in defined laminae of the tectum. Thus, the spatial and temporal expression of three distinct RPTP subtypes--CRYPalpha, CRYP-2, and PTPmu--are consistent with the possibility of their involvement in axon growth and guidance of the retinotectal projection.