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Restoration of Retinal Development in Vsx2 Deficient Mice by Reduction of Gdf11 Levels

  • Rosaysela Santos
  • Jeffry Wu
  • Jason A. Hamilton
  • Rita Pinter
  • Robert Hindges
  • Anne L. CalofEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

The visual system homeobox 2 (Vsx2/Chx10) gene is required for proper eye development in vertebrates. In mouse, mutations in Vsx2 cause micro-ophthalmia, optic nerve aplasia, and failed retinal development, as well as aberrant retinal lamination. GDF11, a member of the TGF-β superfamily of signaling molecules known to function as an autocrine negative regulator of sensory neuron neurogenesis, has also been shown to have dramatic effects on retinal development: Absence of Gdf11 results in an increase in numbers of retinal ganglion cells, resulting from changes in the fates of retinal stem/progenitor cells in Gdf11 null retinas. In the present study, we performed genetic manipulations of the GDF11 signaling system to determine whether alterations in Gdf11 activity levels can improve retinal development in Vsx2-null mice. We found that removal of Gdf11 alleles in Vsx2 orJ/orJ mice can rescue retinal development and thickness to a substantial extent, and partially restores the expression of genes important for the development of specific types of retinal neurons. The molecular mechanism(s) by which reduction of Gdf11 activity enables rescue of retinal development in Vsx2 mutant animals is currently being investigated, and should provide important insights for potential treatment of retinal dystrophies.

Keywords

TGF-beta Brn3b Math5 Foxn4 Crx Neurod1 Chx10 Fst Stem/progenitor cell Micro-ophthalmia 

Notes

Acknowledgements

We thank T. Clevenger, R. Asperer, C. Yaramanoglu, and M. Yazdi for technical assistance and K. Gokoffski, S. Kawauchi, and P. Hollenbeck for comments on the manuscript. This study was supported by grants from the Foundation Fighting Blindness (BR-CMM-0507-0380-UCI) and NIH (DC03583, GM076516) to ALC, and MRC G0601182 to RH. RS received the Young Investigator Travel Award by the National Eye Institute (NIH) to attend the XIVth International Symposium on Retinal Degeneration 2010.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Rosaysela Santos
    • 1
  • Jeffry Wu
    • 1
    • 2
  • Jason A. Hamilton
    • 1
    • 3
  • Rita Pinter
    • 4
    • 5
  • Robert Hindges
    • 4
  • Anne L. Calof
    • 1
    Email author
  1. 1.Department of Anatomy & Neurobiology, Center for Complex Biological SystemsUniversity of CaliforniaIrvineUSA
  2. 2.BOOPT-School of OptometryUniversity of CaliforniaBerkeleyUSA
  3. 3.Department of Regenerative MedicineAthersys IncClevelandUSA
  4. 4.MRC Centre for Developmental NeurobiologyKings CollegeLondonUK
  5. 5.Akron Molecules GmbHViennaAustria

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