BMP7 Acts in Murine Lens Placode Development

Abstract

Targeted inactivation of theBmp7gene in mouse leads to eye defects with late onset and variable penetrance (A. T. Dudleyet al.,1995,Genes Dev.9, 2795–2807; G. Luoet al.,1995,Genes Dev.9, 2808–2820). Here we report that the expressivity of theBmp7mutant phenotype markedly increases in a C3H/He genetic background and that the phenotype implicatesBmp7in the early stages of lens development. Immunolocalization experiments show that BMP7 protein is present in the head ectoderm at the time of lens placode induction. Using anin vitroculture system, we demonstrate that addition of BMP7 antagonists during the period of lens placode induction inhibits lens formation, indicating a role for BMP7 in lens placode development. Next, to integrateBmp7into a developmental pathway controlling formation of the lens placode, we examined the expression of several early lens placode-specific markers inBmp7mutant embryos. In these embryos,Pax6head ectoderm expression is lost just prior to the time when the lens placode should appear, while inPax6-deficient (Sey/Sey) embryos,Bmp7expression is maintained. These results could suggest a simple linear pathway in placode induction in whichBmp7functions upstream ofPax6and regulates lens placode induction. At odds with this interpretation, however, is the finding that expression ofsecreted Frizzled Related Protein-2(sFRP-2), a component of the Wnt signaling pathway which is expressed in prospective lens placode, is absent inSey/Seyembryos but initially present inBmp7mutants. This suggests a different model in whichBmp7function is required to maintainPax6expression after induction, during a preplacodal stage of lens development. We conclude thatBmp7is a critical component of the genetic mechanism(s) controlling lens placode formation.