Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection.
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.
Sakuta
Hiraki
H
Division of Molecular Neurobiology, National Institute for Basic Biology and School of Life Science, The Graduate University for Advanced Studies, Myodaiji-cho, Okazaki 444-8787, Japan.
Takahashi
Hiroo
H
Shintani
Takafumi
T
Etani
Kazuma
K
Aoshima
Akihiro
A
Noda
Masaharu
M
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D012160:Retina / Q000196:embryology / Q000502:physiology*; D013477:Superior Colliculi / Q000196:embryology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014795:Visual Pathways / Q000196:embryology / Q000502:physiology*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta