Sfrp1a and Sfrp5 function as positive regulators of Wnt and BMP signaling during early retinal development

Vanessa L. Holly, Sonya A. Widen, Jakub K. Famulski, Andrew J. Waskiewicz

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)192-204
Number of pages13
JournalDevelopmental Biology
Volume388
Issue number2
DOIs
StatePublished - Apr 15 2014

Bibliographical note

Funding Information:
We wish to acknowledge the excellent zebrafish husbandry of Ms. Aleah McCorry. Ms. Laura Pillay was instrumental in assisting with the qPCR experimental designs. Ms. Caroline Cheng shared her expertise in statistical analysis. This research was supported by a discovery grant from NSERC and an operating grant from CIHR. Appendix A

Keywords

  • BMP
  • Coloboma
  • Gdf6
  • Retina
  • Sfrp1
  • Sfrp5
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Sfrp1a and Sfrp5 function as positive regulators of Wnt and BMP signaling during early retinal development'. Together they form a unique fingerprint.

Cite this