BMP7 acts in murine lens placode development

Targeted inactivation of the Bmp7 gene in mouse leads to eye defects with l ate onset and variable penetrance (A. T. Dudley ei al., 1995, Genes Dev. 9, 2795-2807; G. Luo ct al., 1995, Genes Dev. 9, 2808-2820). Here we report t hat the expressivity of the Bmp7 mutant phenotype markedly increases in a C 3H/He genetic background and that the phenotype implicates Bmp7 in the earl y stages of lens development. Immunolocalization experiments show that BMP7 protein is present in the head ectoderm at the time of lens placode induct ion. Using an in vitro culture system, we demonstrate that addition of BMP7 antagonists during the period of lens placode induction inhibits lens form ation, indicating a role for BMP7 in lens placode development. Next, to int egrate Bmp7 into a developmental pathway controlling formation of the lens placode, we examined the expression of several early lens placode-specific markers in Bmp7 mutant embryos. In these embryos, Pax6 head ectoderm expres sion is lost just prior to the time when the lens placode should appear, wh ile in Pax6-deficient (Sey/Sey) embryos, Bmp7 expression is maintained. The se results could suggest a simple linear pathway in placode induction in wh ich Bmp7 functions upstream of Pax6 and regulates lens placode induction. A t odds with this interpretation, however, is the finding that expression of secreted Frizzled Related Protein-2 (sFRP-2), a component of the Wnt signa ling pathway which is expressed in prospective lens placode, is absent in S ey/Sey embryos but initially present in Bmp7 mutants. This suggests a diffe rent model in which Bmp7 function is required to maintain Pax6 expression a fter induction, during a preplacodal stage of lens development. We conclude that Bmp7 is a critical component of the genetic mechanism(s) controlling lens placode formation. (C) 1999 Academic Press.