BMP4 mediates apoptotic cell death in the developing chick eye

The bone morphogenetic protein (BMP) expression in vertebrates suggests a r eiterative function of these molecules during eye development. However, gen etic analysis in mice has provided only partial information. Using the chic k embryo as a model system, we have analyzed possible additional functions of BMP4 during optic cup formation. Here we describe the expression pattern of Bmp4 and Bmp7 and we show that, in contrast to the mouse, the prospecti ve lens placode ectoderm expresses high levels of Bmp4 but no Bmp7. After o ptic vesicle invagination, Bmp4 is expressed in the prospective dorsal neur al retina, where BmprIA, BmprII, and Smad1, components of the BMP4 signal t ransduction 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 apoptosi s, which parallels the expression not only of Bmp4 but also of Msx1 and Msx 2, genes implicated in BMP4-mediated apoptosis. The use of optic vesicle cu ltures as well as in ovo local addition of BMP4 and its antagonist Noggin p roves that the local activity of BMP4 is responsible for programmed cell de ath in the dorsal optic cup. In addition, we show that Noggin is able to re duce the rate of cell proliferation in the dorsal part of the optic cup whe reas BMP4 increases the number of BrdU-positive cells in retina cultures. T hese results provide evidence that BMP4 contributes to eye development by p romoting cell proliferation and programmed cell death.