BMP-7 IS AN INDUCER OF NEPHROGENESIS, AND IS ALSO REQUIRED FOR EYE DEVELOPMENT AND SKELETAL PATTERNING

Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally identified by their ability to induce ectopic bone formatio n. To investigate the function of one of the BMPs, BMP-7, we have gene rated BMP-7-deficient mice using embryonic stem cell technology. BMP-7 -deficient mice die shortly after birth because of poor kidney develop ment. Histological analysis of mutant embryos at several stages of dev elopment revealed that metanephric mesenchymal cells fail to different iate, resulting in a virtual absence of glomerulus in newborn kidneys. In situ hybridization analysis showed that the absence of BMP-7 affec ts the expression of molecular markers of nephrogenesis, such as Pax-2 and Wnt-4 between 12.5 and 14.5 days postcoitum (dpc). This identifie s BMP-7 as an inducer of nephrogenesis. In addition, BMP-7-deficient m ice have eye defects that appear to originate during lens induction. F inally, BMP-7-deficient mice also have skeletal patterning defects res tricted to the rib cage, the skull, and the hindlimbs.