Nature Neuroscience
8, 1301 - 1309 (2005)
Published online: 18 September 2005; | doi:10.1038/nn1547
SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptorJosana Rodriguez1, Pilar Esteve1, 4, Christine Weinl2, 4, José María Ruiz1, Yasmín Fermin1, Françoise Trousse1, 3, Asha Dwivedy2, Christine Holt2
& Paola Bovolenta11
Departamento de Neurobiología del Desarrollo, Instituto Cajal, CSIC, Dr. Arce 37, Madrid 28002, Spain. 2
Department of Anatomy, Cambridge University, Downing Street, University of Cambridge, Cambridge CB2 3DY, UK. 3
Present address: Centre de Biologie du Développement, CNRS/UPS UMR 5547, Univ. P. Sabatier. 31062 Toulouse Cedex 4, France. 4
These authors contributed equally to this work.
Correspondence should be addressed to Paola Bovolenta bovolenta@cajal.csic.es Axon growth is governed by the ability of growth cones to interpret attractive and repulsive guidance cues. Recent studies have shown that secreted signaling molecules known as morphogens can also act as axon guidance cues. Of the large family of Wnt signaling components, only Wnt4 and Wnt5 seem to participate directly in axon guidance. Here we show that secreted Frizzled-related protein 1 (SFRP1), a proposed Wnt signaling inhibitor, can directly modify and reorient the growth of chick and Xenopus laevis retinal ganglion cell axons. This activity does not require Wnt inhibition and is modulated by extracellular matrix molecules. Intracellularly, SFRP1 function requires G protein activation, protein synthesis and degradation, and it is modulated by cyclic nucleotide levels. Because SFRP1 interacts with Frizzled-2 (Fz2) and interference with Fz2 expression abolishes growth cone responses to SFRP1, we propose a previously unknown function for this molecule: the ability to guide growth cone movement via the Fz2 receptor.
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