Fig. 8. A model for the function of Bmp signaling through Bmpr1a/Bmpr1b receptors in the retina. (A) Schematic representation of an early embryonic eye, indicating the sources of Bmp ligands. Black dots represent dorsally localized Bmp4 transcripts (Furuta and Hogan, 1998), arrows indicate Bmp7 from the lens ectoderm (Wawersik et al., 1999) and arrowheads indicate Bmp2 signaling from the retinal pigmented epithelium (Dudley and Robertson, 1997). (B) Expression of the corresponding Bmp receptors in the eye. Bmpr1a is ubiquitously expressed (hatching), whereas Bmpr1b shows a graded expression within the retina with highest levels ventrally (dots). (C) A relative distribution Bmp signaling activity along the retinal dorsoventral (DV) axis, based on P-Smad1/5/8 immunostaining (Fig. 3D). (D,E) Black and gray arrows indicate functions for genes/pathways deduced from the current study and those from previously published studies, respectively. Broken arrows indicate potential interactions. The potential relationships shown here are not intended to imply direct or linear pathways. (D) Relatively high levels of Bmp signaling are required to specify the dorsal program, ultimately leading to proper retinal topographic mapping. Loss of dorsal specification in Bmpr1a^-/fx;Bmpr1b^-/+;Cre mice indicates that signaling activity falls below the threshold required for DV patterning in these mutants. For simplicity, only interactions suggested by genetic evidence are indicated. (E) Lower levels of Bmp signaling are required throughout the retina to maintain normal growth and to initiate neurogenesis. Candidate downstream targets of Bmp signaling include Chx10 and cyclin D1, as well as Fgf15. Potential regulation of Math5 expression by Mapk is, in part, postulated based on studies in Drosophila implying Egfr-Raf-Mapk signaling in the induction of the pro-neural gene atonal.