Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection

J Neurosci. 2006 Oct 18;26(42):10868-78. doi: 10.1523/JNEUROSCI.3027-06.2006.

Abstract

It has been long believed that the anteroposterior (A-P) and dorsoventral (D-V) axes in the developing retina are determined independently and also that the retinotectal projection along the two axes is controlled independently. However, we recently demonstrated that misexpression of Ventroptin, a bone morphogenic protein (BMP) antagonist, in the developing chick retina alters the retinotectal projection not only along the D-V (or mediolateral) axis but also along the A-P axis. Moreover, the dorsal-high expression of BMP4 is relieved by the dorsotemporal-high expression of BMP2 at embryonic day 5 (E5) in the retina, during which Ventroptin continuously counteracts the two BMPs keeping on the countergradient expression pattern, respectively. Here, we show that the topographic molecules so far reported to have a gradient only along the D-V axis and ephrin-A2 so far only along the A-P axis are both controlled by the BMP signal, and that they are expressed in a gradient manner along the tilted axis from E6 on in the developing chick retina: the expression patterns of these oblique-gradient molecules are all changed, when BMP2 expression is manipulated in the developing retina. Furthermore, in both BMP2 knockdown embryos and ephrin-A2-misexpressed embryos, the retinotectal projection is altered along the two orthogonal axes. The expressional switching from BMP4 to BMP2 thus appears to play a key role in the retinal patterning and topographic retinotectal projection by tilting the D-V axis toward the posterior side during retinal development. Our results also indicate that BMP2 expression is essential for the maintenance of regional specificity along the revised D-V axis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / physiology*
  • Chick Embryo
  • Gene Expression Regulation, Developmental / physiology*
  • Mice
  • Retina / embryology
  • Retina / physiology*
  • Superior Colliculi / embryology
  • Superior Colliculi / physiology*
  • Transforming Growth Factor beta / physiology*
  • Visual Pathways / embryology
  • Visual Pathways / physiology*

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta