RT Journal Article
SR Electronic
T1 BMP4 Mediates Apoptotic Cell Death in the Developing Chick Eye
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1292
OP 1301
DO 10.1523/JNEUROSCI.21-04-01292.2001
VO 21
IS 4
A1 Françoise Trousse
A1 Pilar Esteve
A1 Paola Bovolenta
YR 2001
UL http://www.jneurosci.org/content/21/4/1292.abstract
AB The bone morphogenetic protein (BMP) expression in vertebrates suggests a reiterative function of these molecules during eye development. However, genetic analysis in mice has provided only partial information. Using the chick embryo as a model system, we have analyzed possible additional functions of BMP4 during optic cup formation. Here we describe the expression pattern ofBmp4 and Bmp7 and we show that, in contrast to the mouse, the prospective lens placode ectoderm expresses high levels of Bmp4 but no Bmp7. After optic vesicle invagination, Bmp4 is expressed in the prospective dorsal neural retina, where BmprIA,BmprII, and Smad1, components of the BMP4 signal transduction pathway, are also expressed. In toto terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling analysis shows that the dorsal optic cup is the site of a spatiotemporally restricted apoptosis, which parallels the expression not only ofBmp4 but also of Msx1 andMsx2, genes implicated in BMP4-mediated apoptosis. The use of optic vesicle cultures as well as in ovo local addition of BMP4 and its antagonist Noggin proves that the local activity of BMP4 is responsible for programmed cell death in the dorsal optic cup. In addition, we show that Noggin is able to reduce the rate of cell proliferation in the dorsal part of the optic cup whereas BMP4 increases the number of BrdU-positive cells in retina cultures. These results provide evidence that BMP4 contributes to eye development by promoting cell proliferation and programmed cell death.