 | Formation of the endocardial cushions and valves starts with the endothelial cells which line the inside of the heart. Figure A shows a 36 hour old zebrafish heart. The endothelial (endocardial cells) are expressing GFP under control of the tie2 promoter. The myocardium is counterstained with rhodamine-phallodin. The blue arrow (in all frames) points to the lumen of the atrium. At this stage, the endocardial cells are regularly arrayed within the heart. |
| In figures B and C, at 48 hours, endocardial cells are coalescing at the boundary of the atrium and ventricle. It is not known if this is due to localized proliferation of cells or due to migration of cells from the chambers. |
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| By 60 hours (figure D), some of the cells at the atrioventricular boundary are sending processes into the space between the endocardial and myocardial layers in anticipation of epithelial-mesenchymal transformation. |  |
 | By 96 hours (figure E), bushy cushions of endocardial cells have formed at the AV boundary. Note that even by this time, there is no evidence of true valves in the heart - the 3-dimensional nature of the cushions serves to function as a valve, yet true leaflets have not yet developed. |
Therefore, a number of questions remain to be resolved here: - when do the valves form and what do they look like?
- what developmental mechanisms (division, migration, apoptosis) are used to form the cushions and valves?
- what is the origin of the cells and material which constitute the mature valve leaflets?
Answering these questions will not only provide direct information about valve development, but will be necessary before more advanced questions can be asked about the molecules needed for cushion/valve development. For example, a number of labs have been studying the role of various molecules (ethanol, cyclosporin) on valve development in zebrafish, but they have been assaying for valve development before leaflets have formed. All of these studies need to be repeated in a temporally more appropriate manner. |
