The importance of BMP signaling in the development of vertebrate optic vesicle has been shown repeatedly by gene inactivation and gain-of-function approaches in mice and avian systems. Together these studies demonstrated that the proper balance of BMP signaling is required for proper morphogenesis and differentiation of the retina, lens, and optic stalk.
28 30 31 32 34 35 36 70 71 72 Results in the present study provide further support for this general conclusion. Overexpression of
Msx2 suppressed
Bmp4 expression in the transgenic optic vesicle before lens induction, whereas
Bmp7 expression was upregulated. Results of TUNEL indicated that the loss of
Bmp4 expression may be due to induced apoptosis of
Bmp4-expressing cells instead of transcriptional suppression.
73 74 Because the
Msx2 transgene is not expressed in the ventral portion of the optic vesicle, the increase in expression level and the dorsal expansion of the
Bmp7 expression domain is most likely an indirect effect of
Msx2 overexpression. We speculated that the induced
Bmp7 expression partially complements the loss of
Bmp4, to allow lens induction to go forward and thus the formation of a small optic cup. Alternatively,
Msx2 may possess its own lens induction activity in the absence of BMP4 when it is expressed at appropriate levels. Furuta and Hogan
28 have shown that eye development in
Bmp4 null mutants was arrested before lens induction.
Msx2 expression was not detectable in the optic vesicles of the
Bmp4 null mutant. After the implantation of exogenous BMP4,
Msx2 expression was restored in the
Bmp4 null optic vesicle, and lens induction occurred.
28 In contrast to induction of
Bmp7 expression in the optic vesicle of
Msx2 transgenic embryo,
Bmp7 expression was not altered in the
Bmp4 null mutant optic vesicle. Recently, Hung et al.
36 have shown that lens specific ectopic expression of
Bmp7 can induce
Msx2 expression in the developing neuroretina. Together, these results suggest that
Msx2 and
Bmp7 indirectly regulates the expression of each other.