Sfrp1a and Sfrp5 function as positive regulators of Wnt and BMP signaling during early retinal development.
Axial patterning of the developing eye is critically important for proper axonal pathfinding as well as for key morphogenetic events, such as closure of the optic fissure. The dorsal retina is initially specified by the actions of Bone Morphogenetic Protein (BMP) signaling, with such identity subsequently maintained by the Wnt-β catenin pathway. Using zebrafish as a model system, we demonstrate that Secreted frizzled-related protein 1a (Sfrp1a) and Sfrp5 work cooperatively to pattern the retina along the dorso-ventral axis. Sfrp1a/5 depleted embryos display a reduction in dorsal marker gene expression that is consistent with defects in BMP- and Wnt-dependent dorsal retina identity. In accord with this finding, we observe a marked reduction in transgenic reporters of BMP and Wnt signaling within the dorsal retina of Sfrp1a/5 depleted embryos. In contrast to studies in which canonical Wnt signaling is blocked, we note an increase in BMP ligand expression in Sfrp1a/5 depleted embryos, a phenotype similar to that seen in embryos with inhibited BMP signaling. Overexpression of a low dose of sfrp5 mRNA causes an increase in dorsal retina marker gene expression. We propose a model in which Sfrp proteins function as facilitators of both BMP and Wnt signaling within the dorsal retina.
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
Vanessa L
VL
Holly
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
Sonya A
SA
Widen
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
Jakub K
JK
Famulski
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada. Electronic address: aw@ualberta.ca.
Andrew J
AJ
Waskiewicz
D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017931:DNA Primers; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009024:Morphogenesis; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000196:embryology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*; D000094742:Secreted Frizzled-Related Proteins
D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C515514:Sfrp1a protein, zebrafish; C514540:Sfrp5 protein, zebrafish; D000094742:Secreted Frizzled-Related Proteins
BMP; Coloboma; Gdf6; Retina; Sfrp1; Sfrp5; Wnt