A role for the growth factor Bone Morphogenetic Protein 7 in early development of the murine eye

The early steps of mouse eye development involve a series of inductive interactions between the optic vesicle and adjacent head ectoderm. Signals from the optic vesicle induce a thickening of the head ectoderm known as the lens placode, which ultimately invaginates to form the adult lens. However, while necessary for lens induction, the optic vesicle is not sufficient, as additional signals are required to establish the ectoderm's ability to respond to lens-inducing stimuli. Thus, rather than resulting from a single signaling event, lens induction is coordinated by a sequence of signals combining to govern eye formation. The experiments described here identify a role for Bmp7, a member of the Bone Morphogenetic Protein (BMP) family of growth factors, as one of these regulators of mouse lens placode induction. Previous studies show that targeted inactivation of Bmp7 leads to eye defects with late onset and variable expressivity. However, I demonstrate a marked increase in the severity of the Bmp7 mutant phenotype in a C3H/He genetic background. This increased expressivity has allowed analysis of Bmp7's role in early lens development.;To integrate Bmp7 into a genetic pathway controlling lens placode formation, the expression of early lens placode-specific markers was examined in embryos mutant either for Bmp7 or for the transcription factor Pax6, which is critical for lens placode induction. These experiments suggest a model in which Bmp7 is not required for lens placode induction, but is necessary immediately thereafter, during a pre-placodal stage of lens development. Since Bmp7 and its receptors are widely expressed in the eye-forming region, it is unclear whether the observed lens placode defects reflect Bmp7 function in the head ectoderm, the optic vesicle, or both. To address this question, a tissue recombination system was used to show that Bmp7−/− optic vesicle cannot induce lenses in wild-type ectoderm, nor can wild-type optic vesicle instruct lens induction in Bmp7−/− ectoderm. Thus, Bmp7 is required tissue autonomously in both the lens ectoderm and the optic vesicle, suggesting multiple roles for Bmp7 in early oculogenesis.