Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain

摘要

Animal cells need to be able to communicate with each other so that they can work together in tissues and organs. To do so, cells release signaling molecules that can move around within a tissue and be detected by receptors on other cells. We tend to assume that the signaling molecules are evenly distributed across a tissue and affect all the receiving cells in the same way. However, random variations (noise) that affect how many of these molecules are produced, how they move through the space between cells and how they bind to receptors makes the reality much more complex. Cells responding to the signal somehow can ignore this noise and establish sharp boundaries between different cell types so that neighboring cells have distinct roles in the tissue. Few studies have attempted to measure such noise or address how cells manage to respond to noisy signals in a consistent manner. Retinoic acid is a signaling molecule that plays an important role in the development of the brain in animal embryos. It forms a gradient along the body of the embryo from the head end to the tail end, but it has proved difficult to measure this gradient directly. Sosnik et al. exploited the fact that this molecule is weakly fluorescent and used microscopy to directly detect it in zebrafish embryos. The experiments show that retinoic acid forms a gradient in the embryos, with high levels at the tail end and lower levels at the head end. Sosnik et al. also found that there is a large amount of noise in the retinoic acid gradient. Two cells in the same position can have very different retinoic acid levels, and the levels in a particular cell can vary from one minute to the next. The experiments also show that proteins that interact with retinoic acid help to reduce noise within a cell. This noise reduction is important for sharpening the boundaries between different brain regions in the embryo to allow the brain to develop normally. A future challenge will be to see if similar retinoic acid gradients and noise control occur in other tissues, and if the noise has any positive role to play in development.