In situ analysis of the chicken cSox2 gene, a member of the transcription factor family containing an Sry-like high-mobility group (HMG) box, demonstrated localized expression in the embryonic endoderm. Transcripts of cSox2 appeared before commencement of morphogenesis and cytodifferentiation in the rostral gut epithelium from the pharynx to the stomach. The caudal limit of cSox2 expression coincided with that of the region competent for proventricular differentiation and to the rostral limit of the domain of CdxA, a homologue of Drosophila caudal. During morphogenesis, the level of transcripts of cSox2 decreased in epithelia invaginating into surrounding mesenchyme to form glandular or tubular structures, such as the primordia of the thyroid and lung, glandular epithelium of the proventriculus, and secondary bronchus of the lung. Tissue recombination experiments demonstrated that cSox2 expression is regulated by the underlying mesenchyme as well as morphogenesis and cytodifferentiation. The results suggest that cSox2 plays pivotal roles in generating morphologically and physiologically distinct types of epithelial cells in the gut.

SUMMARY The coronary vessels and epicardium arise from an extracardiac rudiment called the proepicardium. Failed fusion of the proepicardium to the heart results in severe coronary and heart defects. However, it is unknown how the proepicardium protrudes toward and attaches to the looping heart tube. Here we show that ectopic expression of BMP ligands in the embryonic myocardium can cause proepicardial cells to target aberrant regions of the heart. Additionally, misexpression of a BMP antagonist, Noggin, suppresses proepicardium protrusion and contact with the heart. Finally, proepicardium explant preferentially expands toward a co-cultured heart segment. This preference can be mimicked by BMP2/4 and suppressed by Noggin. These results support a model in which myocardium-derived BMP signals regulate the entry of coronary progenitors to the specific site of the heart by directing their morphogenetic movement.

Aims-To investigate the adhesion characteristics of several intraocular lenses (IOLs) to the simulated and rabbit lens capsule. Methods-Adhesive force to bovine collagen sheets was measured in water with polymethylmethacrylate (PMMA), three piece silicone, and acrylic foldable IOLs. In rabbit eyes, phacoemulsification and IOL implantation were performed. Three weeks later, adhesion between the anterior/posterior capsules and IOL optic was tested, and the capsule was examined histologically. Conclusions-The acrylic foldable IOL adhered to the lens capsule more than the PMMA IOL, and the silicone IOL showed no adhesiveness. These diVerences seem to play a role in preventing lens epithelial cells from migrating and forming posterior capsule opacification. (Br J Ophthalmol 1998;82:549-553) Results-The

CAN was characterized by progressive injury to the renal microvasculature and the development of renal scarring. In particular, injury, angioregression and progressive loss of the PTC network strongly contributed to the development of interstitial fibrosis and graft dysfunction in CAN, and might play a crucial role in the development of CAN.

Abstract-This study tested the hypothesis that coronary tubulogenesis and coronary artery formation require VEGF family members. Quail embryos were injected with soluble vascular endothelial growth factor (VEGF) receptors R1 (Flt-1), R2 (Flk-1), R3 (Flt-4), VEGF-Trap (a chimera of R1 and R2), or neutralizing antibodies to VEGF-A, VEGF-B, or fibroblast growth factor (FGF)-2. Our data document that tubulogenesis is temporally dependent on multiple VEGF family members, because the early stage of tubulogenesis was markedly inhibited by VEGF-Trap and to a lesser extent by soluble VEGFR-1. Some inhibition of tubulogenesis was documented when anti-FGF-2, but not anti-VEGF-A, antibodies were injected at embryonic day 6 (E6). Most importantly, we found that VEGF-Trap injected at either E6 or E7 prevented the formation of coronary arteries. Soluble VEGFR-1 and soluble VEGFR-2 modified the formation of coronary arteries, whereas soluble VEGFR-3 was without effect. Antibodies to VEGF-B, but not VEGF-A, had a strong inhibitory effect on coronary artery development. The absence of coronary artery stems, and thus a functional coronary circulation, in the embryos injected with VEGF-Trap caused an accumulation of erythrocytes in the subepicardium and muscular interventricular septum. Using retroviral cell tagging, we showed that some of the erythrocytes in blood islands and small vascular tubes were progeny of the proepicardium. Thus, another salient finding of this study is the first definitive documentation of proepicardially derived hemangioblasts, which can differentiate into erythrocytes. 2 ) All of the cells that contribute to the coronary vasculature (endothelial, smooth muscle, pericytes, and fibroblasts) migrate to the heart from the proepicardium, a transitional structure located posterior to the septum transversum. 3,4 The cells of the proepicardial organ form the epicardium and subepicardium and undergo epithelial-mesenchymal transformation (reviewed by Olivey et al 5 ). Recent evidence shows that hematopoietic precursors, ie, CD45 ϩ cells, are also present on the surface of the quail heart in blood islands before vascularization of the myocardium. 6 Migration of angioblasts into the myocardium and their assembly into vascular tubes constitutes the process of vasculogenesis and is followed by tubular expansion via branching (angiogenesis). Subsequent to these events, a capillary-like network (peritruncal ring) surrounding the base of the outflow tract fuses and penetrates the aorta at 2 specific sites, recruits smooth muscle cells, and consequently forms the 2 main coronary arteries. [7][8][9] The remainder of the endothelial strands in contact with the aorta disappear. 10 It is only at this point in time, E8 to E9 in the quail, 10 that the coronary vasculature is perfused by blood from the aorta. The development of a venous system, like that of the capillary network, also develops before the coronary perfusion from the aorta. 1 Thus, these events are not flow dependent.We have documented the roles of several key gr...