Fig. 1. Lack of BMP signaling leads to microphthalmia. Embryos were infected at HH stage 9-11 with retrovirus expressing either alkaline phosphatase (AP; A,C,F,H,I,L,N,P,R,T) or the BMP-binding protein noggin (B,D,E,G,J,K,M,O,Q,S,U), and studied at E6. (A-E) Gross morphology. Noggin-infected eyes (B) appeared much smaller and less pigmented than alkaline phosphatase controls (A). In histological sections, alkaline phosphatase-infected controls (C) showed no gross abnormalities, while noggin-infected eyes contained rudimentary lens (D, arrow) and neural retina, pigment epithelium, and optic stalk (E, arrowhead). C and D are the same magnification. (F,G) Expression of PROX1 in the lens. Few irregularly distributed PROX1-positive nuclei are scattered throughout the lens of noggin-infected eyes (G), but are more abundant and regularly arranged in alkaline phosphatase-infected controls (F). (H-K) Expression of the pigment-epithelial marker MMP115. Despite the abnormal configuration of the eye in noggin-infected embryos, some pigment epithelium differentiation was apparent both in the presence of pigmented cells (K) and immunoreactivity for MMP115 (J). However, these cells appear less well organized than their counterparts in alkaline phosphatase-infected controls (H,I). (L-U) Expression of neural retina-specific markers. Retinal-specific markers, such as PAX6, islet 1, visinin, and BRN3A, were found in both alkaline phosphatase- (L,N,P,R) and noggin-infected eyes (M,O,Q,S). Positive cells were scarcer and less regularly distributed in noggin-infected eyes. (T,U) Ganglion cell axons. Fibers immunoreactive with the NAPA73 antibody, which is specific for ganglion cell axons, appeared less abundant in noggin-infected eyes, in which they followed abnormal trajectories into the neuroepithelium (arrow U). AP, alkaline phosphatase-infected; Nog, noggin-infected; MMP, MMP115, ISL1; islet 1; VIS, visinin; NAPA, NAPA73. Scale bars: A,B, 50 µm; C,D, 500 µm; E, 50 µm; F-U, 50 µm.