Using cutting-edge imaging technology, UCI biologists have determined that uncontrolled fluctuations (known as “noise”) in the concentration of the vitamin A derivative retinoic acid can lead to disruptions in brain organization during development. Identifying how a cell responds to a signal made by another cell, despite the level of noise present, may improve our understanding of developmental disorders, according to study leader Thomas F. Schilling, professor and chair of developmental & cell biology, and colleagues. During development, retinoic acid is an important secreted molecule that aids in the proper organization of the brain. To measure fluctuations in RA and determine how cells respond to the proper amount despite the presence of constant noise, the researchers used fluorescence lifetime imaging to identify a protein within developing cells that interacts with RA to help reduce the noise. When this protein was altered, cells could no longer control the level of noise within the RA gradient, which led to disruptions in brain organization. With this, the researchers concluded that noise reduction within cells is critical for the proper response to the RA gradient and normal organization of the brain. Study results appear online at eLife.

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