SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor.
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(alpha) 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.
Rodriguez
Josana
J
Departamento de Neurobiología del Desarrollo, Instituto Cajal, CSIC, Dr. Arce 37, Madrid 28002, Spain.
Esteve
Pilar
P
Weinl
Christine
C
Ruiz
José María
JM
Fermin
Yasmín
Y
Trousse
Françoise
F
Dwivedy
Asha
A
Holt
Christine
C
Bovolenta
Paola
P
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005353:Fibronectins / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology; D013997:Time Factors; D014795:Visual Pathways / Q000196:embryology / Q000378:metabolism; D014982:Xenopus laevis; D000099274:Frizzled-Related Proteins
D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D009025:Morpholines; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D000099274:Frizzled-Related Proteins