Role of Bone Morphogenic Protein 2 in Retinal Patterning and Retinotectal Projection

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.

An essential role for Radar (Gdf6a) in inducing dorsal fate in the zebrafish retina

“…Heterozygous Bmp4 ϩ/Ϫ mouse mutants show ocular malformations that appear unrelated to dorsal-ventral patterning (9). A related factor, Bmp2 (Bmp2b in zebrafish) (11) has also been implicated in dorsal patterning of the retina by virtue of its restricted expression in the dorsal retina and its gain-of-function phenotype (12). However, similar to Bmp4, Bmp2 may not be necessary, or even sufficient under physiological conditions, to induce dorsal retinal cell fate.…”

A novel genetic variant of BMP2K contributes to high myopia

“…Besides profound influences of TGFb on scleral remodeling and myopia, expression of BMPs, including BMP2 molecule and BMPs associated components, has also been responsible for ocular globe patterning and remodeling (29,30). From RT-PCR and Northern blot analysis, BMP2 appeared in mouse retina neurons, retinal pigmented epithelium, and human optic nerve head (22,39).…”

“…In search for regulated factors accounting for variation of eye size, BMP2 is a crucial candidate for retinal development and patterning (29,30). Our study evaluates whether a novel protein BMP2-inducible kinase (BMP2K, BIKe), whose expression is up-regulated during BMP2 induction (31), is correlated with high myopia.…”

Feathers with Ocular Architecture: Implications for Functional and Evolutionary Similarities of Visual Signals and Receptors

“…Thus, Hedgehog (Hh) and bone morphogenetic (BMP) family proteins are not always linked the way they are in eyes and in feathers, suggesting that this particular interaction may have been present in an ancestral structure. However, a greater variety of BMP proteins are implicated in eye (BMP2, 4, 7;Murali et al 2005;Sakuta et al 2006) than in feather (BMP2; Harris et al 2005) development, and their action differs (promoting formation of photoreceptors, but inhibiting formation of feather buds and branches). These differences are consistent with separate origins, but the known details of signaling pathways are indecisive.…”